OBJECTIVE To preliminarily investigate the antiasthmatic effect and mechanism of Ephedrae Herba-Armeniacae Semen Amarum herb pair on the respiratory center. METHODS Male SD rats were randomly divided into blank group， model group， dexamethasone group （positive control）， and Ephedrae Herba-Armeniacae Semen Amarum 2∶1， 1∶1 and 1∶2 groups. Rats in each group were administered different ratios of the herb pair decoction [all at 18 g （crude drug）/kg]， dexamethasone suspension （0.5 mg/kg）， or normal saline intragastrically twice daily for seven consecutive days. Forty minutes after the last administration， medicated cerebrospinal fluid was collected to determine the content of effective components entering the brain. One and a half hours after the last administration， the nucleus tractus solitarius （NTS） was located using a stereotaxic apparatus. Histamine phosphate （1 μL） was injected into the NTS region at a constant rate of 1 μL/min using a 10 μL microsyringe to induce excitation of the respiratory center in rats； the blank group was injected with normal saline. The contents of neurotransmitters [nerve growth factor （NGF）， substance P （SP）， norepinephrine （NA）， 5-hydroxytryptamine （5-HT） and acetylcholine （Ach）] in the medulla oblongata brain tissue were detected. The mRNA expressions of neurokinin-1 receptor （NK-1R）， p38 mitogen-activated protein kinase （MAPK）， and c-fos in the medulla oblongata， as well as the protein expressions of NK-1R， p38 MAPK， and c-fos in the NTS region， were determined. RESULTS The main active components of Ephedrae Herba-Armeniacae Semen Amarum herb pair entering the brain were ephedrine， pseudoephedrine， and methylephedrine. Compared with blank group， the contents of NGF， SP， NA， 5-HT and Ach， and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein were significantly increased in the model group （ P ＜0.01）. Compared with model group， Ephedrae Herba-Armeniacae Semen Amarum herb pair groups with different ratios significantly reduced the neurotransmitter contents and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein （ P ＜0.01）， with the 2∶1 Ephedrae Herba-Armeniacae Semen Amarum herb pair and 1∶1 mass ratios showing relatively better effects. CONCLUSIONS Ephedrae Herba alkaloids are the main active components in affecting the function of the respiratory center. The herb pair groups with a larger proportion of Ephedrae Herba exhibit stronger effects. Ephedrae Herba-Armeniacae Semen Amarum herb pair can reduce the excitability of the respiratory center by down-regulating the expression of the NK-1R/MAPK/c-fos pathway in the NTS and decreasing the abnormal release of neurotransmitters such as NGF and SP.

Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Acute kidney injury (AKI) usually requires renal replacement therapy (RRT). Common RRT modes include peritoneal dialysis, continuous renal replacement therapy, intermittent hemodialysis and continuous low-efficiency hemodialysis. In clinical practice, there is still controversy over how to select the appropriate RRT mode for AKI patients and when initiating RRT is more beneficial for AKI patients. This article summarizes previous studies on the impact of RRT mode and initiation timing on the prognosis of AKI patients, with the aim of providing assistance for clinical decision-making.

Objective To study the characteristics of animal models of pulmonary fibrosis so as to provide a reference for the standardization of such models,and to guide research on the pathogenesis,diagnosis,and treatment of pulmonary fibrosis.Methods Studies using experimental pulmonary fibrosis in animals published in the past 10 years were retrieved from the CNKI,Wanfang,VIP,SinoMed,and PubMed databases.Factors including animal species,sex,modeling method,and detection index were summarized,and the data were analyzed using Excel.Results A total of 292 eligible studies were included.The animals mainly included SD rats,Wistar rats,and C57BL/6 mice,and most were male.The most common modeling drugs were bleomycin,paraquat,and silica suspension,mainly administered by intratracheal injection,with a typical modeling cycle of 28 d.The detection indexes mainly comprised lung tissue pathology and measurements of protein expression,cytokine levels,and biochemical indexes.Conclusions SD rats and C57BL/6 mice were the most commonly used animals for experimental pulmonary fibrosis,and intratracheal injection of bleomycin(5 mg/kg)was the most frequently used modeling method.This approach allows for the straightforward and effective replication of pathological features resembling human pulmonary fibrosis,and may serve as a reference for future experimental studies using animal models of pulmonary fibrosis.

Emotional blunting leads to significant declines in cognitive function and activities of daily living in patients with Parkinson's disease, thereby impacting their quality of life and increasing the caregiver burden. Emotional blunting is a progressive condition, and early detection and intervention can slow its progression, making it necessary to assess emotional blunting in patients early. Currently, there are various tools for assessing emotional blunting, but there is a lack of evidence to guide tool selection. This review discusses the impact of emotional blunting on patients with Parkinson's disease and reviews existing assessment tools for emotional blunting, including their content, applications, advantages, and limitations. It also summarizes issues in the application of these tools and offers future directions, aiming to provide a basis for the identification and assessment of emotional blunting in Parkinson's disease patients.

Objective To investigate the effects of glycerol ingestion on pure tone audiometry(PTA),distor-tion products otoacoustic emission(DPOAE),and electrocochleography(ECochG)in patients with Ménière disease(MD).Methods Glycerol test was conducted in 50 patients with MD.PTA was performed in four series:before glycerol intake,1,2 and 3 hours after intake.DPOAE and ECochG were performed before glycerol intake and 2 hours after intake.All results were analyzed to assess the effect of glycerol on cochlear function of patients with MD.Results ① 55％of MD patients tested positive in PTA glycerol test,and the positive rate increased gradually after 1-3 hours of glycerin ingestion(P＜0.05).For the 33 positive ears,the pure tone threshold decreased the most between 1-2 hours and reached the lowest thresholds at 3 hours.Thresholds at 0.5 kHz,1 kHz,2 kHz dropped the most.② The positive rate of DPOAE glycerol test was 56.67％,with 34 positive ears showing a sig-nificant increase in amplitude between 0.75-2 kHz of f2.③ The positive rate of ECochG glycerin test was 13.64％.The decrease of-SP/AP ratio was not statistically significant before and after ingestion of glycerin(P＞0.05).Conclusion Ingestion of glycerin could alter to varying degrees of the results of PTA,DPOAE and ECo-chG,and influence the cochlear function to some extent.

Acute kidney injury (AKI) usually requires renal replacement therapy (RRT). Common RRT modes include peritoneal dialysis, continuous renal replacement therapy, intermittent hemodialysis and continuous low-efficiency hemodialysis. In clinical practice, there is still controversy over how to select the appropriate RRT mode for AKI patients and when initiating RRT is more beneficial for AKI patients. This article summarizes previous studies on the impact of RRT mode and initiation timing on the prognosis of AKI patients, with the aim of providing assistance for clinical decision-making.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

OBJECTIVE: Rhei Radix et Rhizoma has five types of products, namely, raw rhubarb (RR), wine rhubarb (WR), vinegar rhubarb (VR), cooked rhubarb (CR), and rhubarb charcoal (RC). However, Rhei Radix et Rhizoma is easily contaminated with fungi and mycotoxins if not harvested or processed properly. Here, we intend to analyze how microbiome assemblies and co-occurrence patterns are influenced by sampling locations and processing methods. METHODS: High-throughput sequencing and internal transcribed spacer 2 (ITS2) were carried out to study the diversities (α- and β-diversity), composition (dominant taxa and potential biomarkers), and network complexitity of surface fungi on RR, WR, VR, CR, and RC collected from Gansu and Sichuan provinces, China. RESULTS: The phyla Ascomycota and Basidiomycota; the genera Kazachstania, Malassezia, and Asterotremella; and the species Kazachstania exigua, Asterotremella pseudolonga, and Malassezia restricta were the dominant fungi and exhibited differences in the two provinces and the five processed products. The α-diversity and network complexity were strongly dependent on processing methods. Chao 1, the Shannon index, and network complexity and connectivity were highest in the CR group. The α-diversity and network complexity were influenced by sampling locations. Chao 1 and network complexity and connectivity were highest in the Gansu Province. CONCLUSION The assembly and network of the surface microbiome on Rhei Radix et Rhizoma were shaped by processing methods and sampling locations. This paper offers a comprehensive understanding of microorganisms, which can provide early warning for potential mycotoxins and ensure the safety of drugs and consumers.