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Background: Colony‐stimulating factor 1 receptor (CSF1R)‐related disorder (CRD) is a rare autosomal dominant disease. The clinical and genetic characteristics of Chinese patients have not been elucidated. Objective: The objective of the study is to clarify the core features and influence factors of CRD patients in China. Methods: Clinical and genetic‐related data of CRD patients in China were collected. Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Sundal MRI Severity Score were evaluated. Whole exome sequencing was used to analyze the CSF1R mutation status. Patients were compared between different sexes, mutation types, or mutation locations. Results: A total of 103 patients were included, with a male‐to‐female ratio of 1:1.51. The average age of onset was (40.75 ± 8.58). Cognitive impairment (85.1%, 86/101) and parkinsonism (76.2%, 77/101) were the main clinical symptoms. The most common imaging feature was bilateral asymmetric white matter changes (100.0%). A total of 66 CSF1R gene mutants (22 novel mutations) were found, and 15 of 92 probands carried c.2381 T > C/p.I794T (16.30%). The MMSE and MoCA scores (17.0 [9.0], 11.90 ± 7.16) of female patients were significantly lower than those of male patients (23.0 [10.0], 16.36 ± 7.89), and the white matter severity score (20.19 ± 8.47) of female patients was significantly higher than that of male patients (16.00 ± 7.62). There is no statistical difference in age of onset between male and female patients. Conclusions: The core manifestations of Chinese CRD patients are progressive cognitive decline, parkinsonism, and bilateral asymmetric white matter changes. Compared to men, women have more severe cognitive impairment and imaging changes. c.2381 T > C/p.I794T is a hotspot mutation in Chinese patients. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

The dynamic stability of dense medium suspension is the premise to ensure the effective separation of mineral particles in the separation equipment. It is usually difficult to directly measure the dynamic stability of the suspension in the separation process of the dense medium cyclone. In this paper, a parameter defined as the density difference value between the underflow and overflow of cyclone is used to characterize the dynamic stability of the suspension in the separation process. Under the conditions of different operating parameters and structural parameters, the influencing factors of the dynamic stability of 1.30–1.60 g/cm3 dense medium suspension are systematically studied. The results show that the parameter value is in the range of 0.20–0.50 g/cm3, which is conducive to the separation of particles. When the suspension density increases, the characteristic value of density difference decreases, the influence of the suspension density, feed pressure, the diameter of underflow and overflow port diameter on the density difference characteristic are also researched. Eventually, the formula for calculating the density difference of the characteristic value of suspension is derived. [ABSTRACT FROM AUTHOR]

Aim: To assess the safety, tolerability, pharmacokinetics (PKs) and pharmacodynamics of HRS‐7535, a novel glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), in healthy participants. Materials and Methods: This phase 1 trial consisted of single‐ascending dose (SAD), food effect (FE) and multiple‐ascending dose (MAD) parts. In the SAD part, participants were randomized (6:2) to receive HRS‐7535 (at doses of 15, 60 and 120 mg; administered orally once daily) or placebo. In the FE part, participants were randomized (8:2) to receive a single dose of 90‐mg HRS‐7535 or placebo, in both fed and fasted states. In the MAD part, participants were randomized (18:6) to receive daily HRS‐7535 (120 mg [30/60/90/120‐mg titration scheme]) or placebo for 28 days. The primary endpoints were safety and tolerability. Results: Nausea and vomiting were the most frequently reported AEs across all three parts. In the SAD part, the median Tmax was 5.98‐5.99 hours and the geometric mean t1/2 was 5.28‐9.08 hours across the HRS‐7535 dosing range. In the MAD part, the median Tmax was 5.98‐10.98 hours and the geometric mean t1/2 was 6.48‐8.42 hours on day 28 in participants on HRS‐7535. PKs were approximately dose‐proportional. On day 29 in the MAD part, the mean (percentage) reduction in body weight from baseline was 4.38 kg (6.63%) for participants who received HRS‐7535, compared with 0.8 kg (1.18%) for those participants who received a placebo. Conclusions: HRS‐7535 exhibited a safety and tolerability profile consistent with other GLP‐1RAs and showed PKs suitable for once‐daily dosing. These findings support further clinical development of HRS‐7535 for type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion More than 60% of paroxysmal kinesigenic dyskinesia (PKD) cases are of uncertain variants.The aim was to elucidate novel genetic contribution to PKD.A total of 476 probands with uncertain genetic causes were enrolled for whole‐exome sequencing. A method of case–control analysis was applied to identify the candidate genes. Whole‐cell patch‐clamp recording was applied to verify the electrophysiological impact of the identified variants. A mouse model with cerebellar heterozygous knockout of the candidate gene was developed via adeno‐associated virus injection, and dystonia‐like phenotype inducement and rotarod tests were performed. In vivo multiunit electrical recording was applied to investigate the change in neural excitability in knockout mice.Heterozygous variants of potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) clustered in PKD patients were compared with those in the control groups. Fifteen variants were detected in 16 of 522 probands (frequency = 3.07%). Patients with KCNJ10 variants tended to have a milder manifestation compared to those with PRRT2 (proline‐rich transmembrane protein 2) variants. KCNJ10 variants partially altered the transmembrane location of inwardly rectifying potassium channel 4.1 (Kir4.1). The Kcnj10 expression is consistent with the natural course of PKD. Variants resulted in different degrees of reduction in cell Kir4.1 currents, and mice with heterozygous conditional knockout of Kcnj10 in the cerebellum presented dystonic posture, together with poor motor coordination and motor learning ability in rotarod tests. The firing rate of deep cerebellar nuclei was significantly elevated in Kcnj10‐cKO mice.We identified heterozygous variants of KCNJ10 in PKD. Impaired function of Kir4.1 might lead to abnormal neuronal excitability, which attributed to PKD. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Periodontal disease is widespread among pregnant women, and it is possible that taking action to improve oral health conditions can make improvements in adverse pregnancy outcomes. Herein, we summarize the recent evidence using a network meta-analysis to assess the effects of different periodontal treatment intervention strategies on the risk of adverse pregnancy outcomes in pregnant women., Materials and Methods: Randomized controlled trials were retrieved from PubMed, Web of Science, Embase, and Cochrane Library databases. After literature screening, data extraction, and quality evaluation of the included literature were performed, the R studio 4.2.2 "netmeta" package was used for the network meta-analysis., Results: A total of 20 studies were included, and 5 adverse pregnancy outcomes (preterm birth, low birth weight, preterm birth and/or low birth weight infants, small for gestational age, and pre-eclampsia) were considered to examine the effects of different periodontal treatment interventions strategies on the risk of the abovementioned outcome indicators. The results of the network meta-analysis demonstrated that the three periodontal treatment intervention strategies of sub- and/or supra-gingival scaling and root planing + chlorhexidine rinsing (SRP + CR), sub- and/or supra-gingival scaling and root planing+chlorhexidine rinsing + tooth polishing and plaque control (SRP + CR + TP), and sub- and/or supra-gingival scaling and root planing +sonic toothbrush + tooth polishing and plaque control (SRP + ST + TP) reduced the risk of preterm birth [odds ratio (OR) = 0.29, 95% confidence interval (CI) (0.10-0.88), OR = 0.25, 95CI% (0.10-0.63), OR = 0.28, 95CI% (0.11-0.69), respectively]. In addition, two periodontal treatment intervention strategies, SRP + CR and SRP + CR + TP, were effective methods in terms of the risk of preterm birth and/or low birth weight [OR = 0.18, 95CI% (0.06-0.52), OR = 0.31, 95CI% (0.12-0.79)]., Conclusion: The available evidence suggests that the risk of preterm birth and preterm birth and/or low birth weight can be reduced with certain periodontal treatment intervention strategies. Future studies should focus on optimizing intervention strategies and the optimal timing for different periods of pregnancy, in order to provide a reference for pregnant women's healthcare., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=407901, CRD42023407901., 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 © 2024 Wu, Wu, Tang, Zhang, Wei, Yu, Li, Zhao, Wang, Wu and Hong.)

Purpose: This study aimed to characterize the safety profiles of rivaroxaban-associated suspected adverse events by mining the Food and Drug Administration Adverse Event Reporting System (FAERS)., Methods: A disproportionality analysis of spontaneously reported suspected adverse drug reactions (ADRs) was conducted. The reports in FAERS from 2014 to 2024 were compiled. Frequentist and Bayesian statistics were both applied to calculate drug-AE combinations in system organ classes and preferred-term levels. Reporting odds ratio (ROR), proportional reporting ratio (PRR), the Medicines and Healthcare products Regulatory Agency (MHRA), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) methods were analyzed and used to compare the suspected AEs., Results: Of 77,384 ADR reports, 66,705 (86.20%) were serious rivaroxaban AE reports. The most common age group was above 65 years. The suspected adverse effects of rivaroxaban emerging for system organ classes (SOCs) primarily included "Gastrointestinal disorders"; "Injury, poisoning, and procedural complications", "Nervous system disorders" and "Vascular disorders". Ranked by EBGM, the top signal strength of suspected AE signals of rivaroxaban under ROR algorithm at the preferred-term (PT) level were "Haemorrhagic arteriovenous malformation" ( N = 571, ROR = 756.520, PRR = 754.029, Information Component (IC) = 7.197, Empirical Bayesian Geometric Mean (EBGM) = 146.725), "Gastrointestinal vascular malformation haemorrhagic" ( N = 197, ROR = 211.138, PRR = 210.950, IC = 6.614, EBGM = 97.923), and "Diverticulum intestinal haemorrhagic" ( N = 722, ROR = 169.898, PRR = 169.210, IC = 6.458, EBGM = 97.920). Moreover, uncommon but significantly suspected AE signals, such as "Coagulation factor X level increased", "Basal ganglia haematoma", and "Proctitis haemorrhagic" were observed. Notably, "Gastrointestinal haemorrhage" ( N = 13,436, ROR = 80.477, PRR = 74.460, IC = 5.729, EBGM = 53.042), "Upper gastrointestinal haemorrhage"( N = 2,872, ROR = 73.978, PRR = 72.797, IC = 5.706, EBGM = 52.198) and "Internal haemorrhage" ( N = 2,368, ROR = 91.979, PRR = 80.899, IC = 5.813, EBGM = 56.212) exhibited relatively high occurrence rates and signal strengths. From 2014 to 2024, the IC values of rivaroxaban-associated suspected AEs for "Surgical and medical procedures" and "Cardiac disorders" showed an annual increasing trend in the time-span analysis. Based on the various visulization plots, a key discovery is that "Gastrointestinal hemorrhage" emerged as the most significant suspected AE across five algorithms. The exciting finding was that the MGPS algorithm revealed a higher risk of suspected AEs under the "Investigations" category. However, the results of the analyses of the other algorithms at the SOC level were not akin to this. Moreover, the results of signal mining for the three main types of indication populations with adverse drug reactions (ADRs), including Atrial fibrillation, Cerebrovascular accident prophylaxis, and Deep vein thrombosis were shown that "Gastrointestinal haemorrhage", "Epistaxis", "Haematuria", "Rectal haemorrhage", and "Upper gastrointestinal haemorrhage" were detected as the most common and significant signals of suspected adverse events., Conclusion: Rivaroxaban has risks of various suspected adverse reactions while providing therapeutic effects and being used widely. Our pharmacovigilance study may provide valuable hints that practitioners should closely monitor occurrences of "Gastrointestinal disorders", "Injury, poisoning, and procedural complications" and "Nervous system disorders", and other events in clinical applications. Consequently, it remains to persist in monitoring rivaroxaban, assessing the associated risks in the future., 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 © 2024 Wu, Wu, Tang, Wang, Wei, Zhang, Li, Li, Wang, Wu and Hong.)