Objective: This study aims to investigate may moesin deficiency resulted in neurodevelopmental abnormalities caused by negative impact on synaptic signaling ultimately leading to synaptic structure and plasticity. Methods: Behavioral assessments measured neurodevelopment (surface righting, negative geotaxis, cliff avoidance), anxiety (open field test, elevated plus maze test), and memory (passive avoidance test, Y-maze test) in moesin-knockout mice (KO) compared to wild-type mice (WT). Whole exome sequencing (WES) of brain (KO vs. WT) and analysis of synaptic proteins were performed to determine the disruption of signal pathways downstream of moesin. Risperidone, a therapeutic agent, was utilized to reverse the neurodevelopmental aberrance in moesin KO. Results: Moesin-KO pups exhibited decrease in the surface righting ability on postnatal day 7 (p<0.05) and increase in time spent in the closed arms (p<0.01), showing increased anxiety-like behavior. WES revealed mutations in pathway aberration in neuron projection, actin filament-based processes, and neuronal migration in KO. Decreased cell viability (p<0.001) and expression of soluble NSF adapter protein 25 (SNAP25) (p<0.001) and postsynaptic density protein 95 (PSD95) (p<0.01) was observed in days in vitro 7 neurons. Downregulation of synaptic proteins, and altered phosphorylation levels of Synapsin I, mammalian uncoordinated 18 (MUNC18), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) was observed in KO cortex and hippocampus. Risperidone reversed the memory impairment in the passive avoidance test and the spontaneous alternation percentage in the Y maze test. Risperidone also restored the reduced expression of PSD95 (p<0.01) and the phosphorylation of Synapsin at Ser605 (p<0.05) and Ser549 (p<0.001) in the cortex of moesin-KO. Conclusion Moesin deficiency leads to neurodevelopmental delay and memory decline, which may be caused through altered regulation in synaptic proteins and function.

Objective: This study aims to investigate may moesin deficiency resulted in neurodevelopmental abnormalities caused by negative impact on synaptic signaling ultimately leading to synaptic structure and plasticity. Methods: Behavioral assessments measured neurodevelopment (surface righting, negative geotaxis, cliff avoidance), anxiety (open field test, elevated plus maze test), and memory (passive avoidance test, Y-maze test) in moesin-knockout mice (KO) compared to wild-type mice (WT). Whole exome sequencing (WES) of brain (KO vs. WT) and analysis of synaptic proteins were performed to determine the disruption of signal pathways downstream of moesin. Risperidone, a therapeutic agent, was utilized to reverse the neurodevelopmental aberrance in moesin KO. Results: Moesin-KO pups exhibited decrease in the surface righting ability on postnatal day 7 (p<0.05) and increase in time spent in the closed arms (p<0.01), showing increased anxiety-like behavior. WES revealed mutations in pathway aberration in neuron projection, actin filament-based processes, and neuronal migration in KO. Decreased cell viability (p<0.001) and expression of soluble NSF adapter protein 25 (SNAP25) (p<0.001) and postsynaptic density protein 95 (PSD95) (p<0.01) was observed in days in vitro 7 neurons. Downregulation of synaptic proteins, and altered phosphorylation levels of Synapsin I, mammalian uncoordinated 18 (MUNC18), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) was observed in KO cortex and hippocampus. Risperidone reversed the memory impairment in the passive avoidance test and the spontaneous alternation percentage in the Y maze test. Risperidone also restored the reduced expression of PSD95 (p<0.01) and the phosphorylation of Synapsin at Ser605 (p<0.05) and Ser549 (p<0.001) in the cortex of moesin-KO. Conclusion Moesin deficiency leads to neurodevelopmental delay and memory decline, which may be caused through altered regulation in synaptic proteins and function.

Objective: This study aims to investigate may moesin deficiency resulted in neurodevelopmental abnormalities caused by negative impact on synaptic signaling ultimately leading to synaptic structure and plasticity. Methods: Behavioral assessments measured neurodevelopment (surface righting, negative geotaxis, cliff avoidance), anxiety (open field test, elevated plus maze test), and memory (passive avoidance test, Y-maze test) in moesin-knockout mice (KO) compared to wild-type mice (WT). Whole exome sequencing (WES) of brain (KO vs. WT) and analysis of synaptic proteins were performed to determine the disruption of signal pathways downstream of moesin. Risperidone, a therapeutic agent, was utilized to reverse the neurodevelopmental aberrance in moesin KO. Results: Moesin-KO pups exhibited decrease in the surface righting ability on postnatal day 7 (p<0.05) and increase in time spent in the closed arms (p<0.01), showing increased anxiety-like behavior. WES revealed mutations in pathway aberration in neuron projection, actin filament-based processes, and neuronal migration in KO. Decreased cell viability (p<0.001) and expression of soluble NSF adapter protein 25 (SNAP25) (p<0.001) and postsynaptic density protein 95 (PSD95) (p<0.01) was observed in days in vitro 7 neurons. Downregulation of synaptic proteins, and altered phosphorylation levels of Synapsin I, mammalian uncoordinated 18 (MUNC18), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) was observed in KO cortex and hippocampus. Risperidone reversed the memory impairment in the passive avoidance test and the spontaneous alternation percentage in the Y maze test. Risperidone also restored the reduced expression of PSD95 (p<0.01) and the phosphorylation of Synapsin at Ser605 (p<0.05) and Ser549 (p<0.001) in the cortex of moesin-KO. Conclusion Moesin deficiency leads to neurodevelopmental delay and memory decline, which may be caused through altered regulation in synaptic proteins and function.

Objective: This study aims to investigate may moesin deficiency resulted in neurodevelopmental abnormalities caused by negative impact on synaptic signaling ultimately leading to synaptic structure and plasticity. Methods: Behavioral assessments measured neurodevelopment (surface righting, negative geotaxis, cliff avoidance), anxiety (open field test, elevated plus maze test), and memory (passive avoidance test, Y-maze test) in moesin-knockout mice (KO) compared to wild-type mice (WT). Whole exome sequencing (WES) of brain (KO vs. WT) and analysis of synaptic proteins were performed to determine the disruption of signal pathways downstream of moesin. Risperidone, a therapeutic agent, was utilized to reverse the neurodevelopmental aberrance in moesin KO. Results: Moesin-KO pups exhibited decrease in the surface righting ability on postnatal day 7 (p<0.05) and increase in time spent in the closed arms (p<0.01), showing increased anxiety-like behavior. WES revealed mutations in pathway aberration in neuron projection, actin filament-based processes, and neuronal migration in KO. Decreased cell viability (p<0.001) and expression of soluble NSF adapter protein 25 (SNAP25) (p<0.001) and postsynaptic density protein 95 (PSD95) (p<0.01) was observed in days in vitro 7 neurons. Downregulation of synaptic proteins, and altered phosphorylation levels of Synapsin I, mammalian uncoordinated 18 (MUNC18), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) was observed in KO cortex and hippocampus. Risperidone reversed the memory impairment in the passive avoidance test and the spontaneous alternation percentage in the Y maze test. Risperidone also restored the reduced expression of PSD95 (p<0.01) and the phosphorylation of Synapsin at Ser605 (p<0.05) and Ser549 (p<0.001) in the cortex of moesin-KO. Conclusion Moesin deficiency leads to neurodevelopmental delay and memory decline, which may be caused through altered regulation in synaptic proteins and function.

Objective: This study aims to investigate may moesin deficiency resulted in neurodevelopmental abnormalities caused by negative impact on synaptic signaling ultimately leading to synaptic structure and plasticity. Methods: Behavioral assessments measured neurodevelopment (surface righting, negative geotaxis, cliff avoidance), anxiety (open field test, elevated plus maze test), and memory (passive avoidance test, Y-maze test) in moesin-knockout mice (KO) compared to wild-type mice (WT). Whole exome sequencing (WES) of brain (KO vs. WT) and analysis of synaptic proteins were performed to determine the disruption of signal pathways downstream of moesin. Risperidone, a therapeutic agent, was utilized to reverse the neurodevelopmental aberrance in moesin KO. Results: Moesin-KO pups exhibited decrease in the surface righting ability on postnatal day 7 (p<0.05) and increase in time spent in the closed arms (p<0.01), showing increased anxiety-like behavior. WES revealed mutations in pathway aberration in neuron projection, actin filament-based processes, and neuronal migration in KO. Decreased cell viability (p<0.001) and expression of soluble NSF adapter protein 25 (SNAP25) (p<0.001) and postsynaptic density protein 95 (PSD95) (p<0.01) was observed in days in vitro 7 neurons. Downregulation of synaptic proteins, and altered phosphorylation levels of Synapsin I, mammalian uncoordinated 18 (MUNC18), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) was observed in KO cortex and hippocampus. Risperidone reversed the memory impairment in the passive avoidance test and the spontaneous alternation percentage in the Y maze test. Risperidone also restored the reduced expression of PSD95 (p<0.01) and the phosphorylation of Synapsin at Ser605 (p<0.05) and Ser549 (p<0.001) in the cortex of moesin-KO. Conclusion Moesin deficiency leads to neurodevelopmental delay and memory decline, which may be caused through altered regulation in synaptic proteins and function.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

Climate and land use changes may significantly impact the habitat distribution of Gastrodia elata, an endangered traditional medicinal plant. Accurately predicting its future potential suitable habitats is crucial for its conservation and sustainable development. This study integrates current distribution data of G. elata with 56 environmental variables and uses the MaxEnt model to predict changes in its suitable habitats under current climate conditions and four future climate scenarios(SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). The results show that October precipitation and December minimum temperature are key environmental factors influencing its distribution. Under the current climate, optimal habitats for G. elata are concentrated in montane forest areas in Sichuan, Yunnan, Guizhou, and Hubei, which meet the species' requirements for understory growth. Across all future scenarios, the suitable habitat of G. elata consistently shows a stable northward shift, with a steady increase in suitable areas, extending to the middle and lower reaches of the Yangtze River and the Huang-Huai region, and even expanding into Liaoning, Jilin, and southern Heilongjiang. Land use analysis, taking into account the protection of arable land and the utilization of forest resources, indicates that by 2100, under future climate conditions, arable land in medium-to high-suitability areas is expected to increase by 30%-124%. While the conversion of non-suitable forest land into suitable habitats is projected to increase by 5%-52%, the growth of medium-to high-suitability areas within forests is relatively modest, ranging from 1% to 24%. These findings highlight the need to balance agricultural expansion with forest resource conservation to ensure the long-term sustainability of G. elata and provide scientific guidance for future suitable habitat management.
Ecosystem ; China ; Climate Change ; Gastrodia/growth & development* ; Conservation of Natural Resources ; Plants, Medicinal/growth & development*

OBJECTIVE: To explore the early clinical efficacy of a three-stage external treatment with traditional Chinese medicine (TCM) in the treatment of talar bone contusion caused by acute ankle sprain. METHODS: A retrospective analysis was performed on 360 patients with primary lateral ankle sprain admitted from September 2021 to July 2024. Patients with talar bone contusion were selected based on MRI examination, and 73 cases were finally included. According to different treatment methods, they were divided into the observation group and the control group. The observation group consisted of 35 cases, including 16 males and 19 females, aged 24 to 37 years old with an average of (30.34±2.68) years old, and received the three-stage external TCM treatment combined with the "POLICE" protocol. The control group included 38 cases, including 18 males and 20 females, aged 24 to 35 years old with an average of (29.87±2.57) years old, and was treated with the "POLICE" protocol alone. The volume of bone marrow edema (BME) area shown by MRI before treatment and 6 weeks after treatment was measured using 3D Slicer software, and the BME improvement rate was calculated. The "Figure of 8" measurement method was used to assess ankle swelling before treatment and at 1 and 3 weeks after treatment. The visual analogue scale (VAS) was used to evaluate ankle pain before treatment and at 1 and 6 weeks after treatment. At 6 weeks after treatment, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Karlsson ankle function score system were used to evaluate the improvement of ankle function. RESULTS: A total of 73 patients with talar bone contusion caused by ankle sprain completed the 6-week follow-up. At 6 weeks after treatment, the BME improvement rate in the observation group was (39.18±0.06)%, which was higher than (26.75±0.03)% in the control group, with a statistically significant difference (P<0.05). After 1 week of treatment, the VAS score in the observation group was (2.89±0.72) points, lower than (3.37±0.79) points in the control group, and the difference was statistically significant (P<0.05). The ankle swelling degree in the observation group was (50.20±3.19) cm, lower than (52.00±3.60) cm in the control group, with a statistically significant difference (P<0.05). After 3 weeks of treatment, there was no statistically significant difference in ankle swelling between the two groups. At 6 weeks after treatment, there was no statistically significant difference in VAS scores between the two groups. At 6 weeks after treatment, the AOFAS ankle-hindfoot score and Karlsson score in the observation group were (87.43±4.18) and (82.77±5.93) points, respectively, which were higher than (82.92±4.87) and (76.45±6.85) points in the control group, with statistically significant differences (P<0.05). According to the AOFAS ankle-hindfoot score, 8 cases were excellent and 27 cases were good in the observation group;2 cases were excellent, 33 cases were good, and 3 cases were fair in the control group. The difference between the two groups was statistically significant (χ²=7.089, P=0.029). CONCLUSION The three-stage external TCM treatment combined with the "POLICE" protocol has a significant early clinical efficacy. It can significantly reduce ankle pain and swelling in patients with bone contusion caused by acute lateral ankle sprain, promote the absorption of bone marrow edema, and accelerate the recovery of ankle function.
Ankle Injuries/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Talus/injuries* ; Retrospective Studies ; Administration, Cutaneous ; Magnetic Resonance Imaging ; Humans ; Male ; Female ; Young Adult ; Adult ; Contusions/etiology* ; Visual Analog Scale ; Musculoskeletal Pain/etiology* ; Recovery of Function/drug effects* ; Treatment Outcome ; Follow-Up Studies

Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*