Objective To explore the effect of Mycobacterium tuberculosis infection on the primary cilia of mono-cytse-macrophages and its potential mechanisms of promoting osteoclast differentiation.Methods Bone marrow-de-rived mononuclear cells(BMMCs)isolated from patients in control group and spinal tuberculosis group(TB group)were performed in vitro culture,and then cultured with Mycobacterium tuberculosis,infection model(Rv group)was constructed.Changes in cilia were observed by fluorescence staining and scanning electron microscopy tech-nique,a mouse spinal TB model was constructed for validating.Results Compared with the control group,the ex-pression of primary cili markers in the lesion of bone tissue of patients in TB group decreased significantly;After co-culturing with Mycobacterium tuberculosis,the ratio(48.56％±7.77％vs 9.58％±5.59％)and length(4.050[3.289,4.666]μm vs 0[0,0.676]μm)of primary cilia of monocytes-macrophages in the Rv group decreased sig-nificantly;The infiltration of osteoclasts in the bone marrow cavity of spinal TB mice was obvious,and the propor-tion and length of primary cilia decreased significantly.Conclusion Intracellular infection of Mycobacterium tuberculosis can induce degradation of primary cilia in monocytes-macrophages,promote osteoclast differentiation,and exacerbate vertebral bone resorption.

Objective To explore the effect of Mycobacterium tuberculosis infection on the primary cilia of mono-cytse-macrophages and its potential mechanisms of promoting osteoclast differentiation.Methods Bone marrow-de-rived mononuclear cells(BMMCs)isolated from patients in control group and spinal tuberculosis group(TB group)were performed in vitro culture,and then cultured with Mycobacterium tuberculosis,infection model(Rv group)was constructed.Changes in cilia were observed by fluorescence staining and scanning electron microscopy tech-nique,a mouse spinal TB model was constructed for validating.Results Compared with the control group,the ex-pression of primary cili markers in the lesion of bone tissue of patients in TB group decreased significantly;After co-culturing with Mycobacterium tuberculosis,the ratio(48.56％±7.77％vs 9.58％±5.59％)and length(4.050[3.289,4.666]μm vs 0[0,0.676]μm)of primary cilia of monocytes-macrophages in the Rv group decreased sig-nificantly;The infiltration of osteoclasts in the bone marrow cavity of spinal TB mice was obvious,and the propor-tion and length of primary cilia decreased significantly.Conclusion Intracellular infection of Mycobacterium tuberculosis can induce degradation of primary cilia in monocytes-macrophages,promote osteoclast differentiation,and exacerbate vertebral bone resorption.

Triggering receptor expressed on myeloid cells 2 (TREM2)-mediated microglial phagocytosis is an energy-intensive process that plays a crucial role in amyloid beta (Aβ) clearance in Alzheimer's disease (AD). Energy metabolic reprogramming (EMR) in microglia induced by TREM2 presents therapeutic targets for cognitive impairment in AD. Jiawei Xionggui Decoction (JWXG) has demonstrated effectiveness in enhancing energy supply, protecting microglia, and mitigating cognitive impairment in APP/PS1 mice. However, the mechanism by which JWXG enhances Aβ phagocytosis through TREM2-mediated EMR in microglia remains unclear. This study investigates how JWXG facilitates microglial phagocytosis and alleviates cognitive deficits in AD through TREM2-mediated EMR. Microglial phagocytosis was evaluated through immunofluorescence staining in vitro and in vivo. The EMR level of microglia was assessed using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kits. The TREM2/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway was analyzed using Western blotting in BV₂ cells. TREM2^-/- BV₂ cells were utilized for reverse validation experiments. The Aβ burden, neuropathological features, and cognitive ability in APP/PS1 mice were evaluated using ELISA kits, immunohistochemistry (IHC), and the Morris water maze (MWM) test. JWXG enhanced both the phagocytosis of EMR disorder-BV₂ cells (EMRD-BV₂) and increased EMR levels. Notably, these effects were significantly reversed in TREM2^-/- BV₂ cells. JWXG elevated TREM2 expression, adenosine triphosphate (ATP) levels, and microglial phagocytosis in APP/PS1 mice. Additionally, JWXG reduced Aβ-burden, neuropathological lesions, and cognitive deficits in APP/PS1 mice. In conclusion, JWXG promoted TREM2-induced EMR and enhanced microglial phagocytosis, thereby reducing Aβ deposition, improving neuropathological lesions, and alleviating cognitive deficits.
Drugs, Chinese Herbal/pharmacology* ; Microglia/drug effects* ; Phagocytosis ; Cognitive Dysfunction/drug therapy* ; Metabolic Reprogramming ; Animals ; Mice ; Cell Line ; Receptors, Immunologic/metabolism* ; Membrane Glycoproteins/metabolism* ; Signal Transduction ; Amyloid beta-Peptides/metabolism* ; Energy Metabolism

Gastrointestinal motility disorder is an important cause of digestive system diseases. Patients often suffer from nausea， vomiting， gastric retention， gastroparesis， constipation， and many other symptoms， and their quality of life is seriously reduced. Prokinetic agents are routinely used in clinical practice， but their long-term use is prone to problems such as reduced efficacy and increased adverse reactions. Since the incidence of gastrointestinal diseases has continued to rise globally in recent years， there is an urgent need for clinical development of safe and effective treatment strategies. Aurantii Fructus， a traditional Chinese medicine， has the effect of smoothing Qi and eliminating distention， and it has been used to treat gastrointestinal diseases for thousands of years. In modern clinical practice， it is mainly used for the treatment and auxiliary treatment of various gastrointestinal diseases such as functional dyspepsia， functional constipation， and irritable bowel syndrome. The efficacy is remarkable， and no adverse reactions have been reported at conventional doses. Therefore， it can greatly improve the symptoms of patients with gastrointestinal diseases and improve their quality of life. Modern research has revealed that there are many active components in Aurantii Fructus， among which flavonoids have the highest content and the most types. Flavonoids are the main active components in Aurantii Fructus to regulate gastrointestinal motility. Aurantii Fructus and its active components can affect gastrointestinal hormones， neural pathways， Cajal mesenchymal cells， and other multiple mechanisms. They can adjust gastrointestinal motility and correct gastrointestinal motility disorders， showing potential application value in the treatment of gastrointestinal motility disorders. However， a comprehensive analysis of Aurantii Fructus in this aspect is still lacking. This study summarized the pharmacological activities of active components of Aurantii Fructus extract and its flavonoids， volatile oils， alkaloids， and coumarin on the regulation of gastrointestinal motility and explored the latest research progress on its mechanism. Finally， the adverse reactions of Aurantii Fructus were summarized. It aims to provide a scientific basis for the research and clinical application of Aurantii Fructus and its active components in the regulation of gastrointestinal motility.

Given that the existing methods of enhancing the resolution of magnetic resonance(MR)images by algorithms mainly focus on cross-size and same-size supervised super-resolution algorithms,a super-resolution reconstruction network(SG-Diffusion)for MR images is proposed based on an implicit degradation mapping model.The degradation process of MR images is implicitly modeled through a masked autoencoder,which reduces the domain gap between the experimental constructed dataset and the actual MR images,and the sample pairs are generated based on implicit degradation model.After training,a MR image reconstruction network based on self-guided diffusion model is obtained to realize the spatial resolution enhancement of unsupervised same-size MR images.The results of super-resolution experiments of 4-fold accelerated sampling brain MR images on fastMRI dataset show that the MR image super-resolution reconstruction network based on implicit degradation model proposed in the study can effectively improve the spatial resolution of degraded MR images,and that compared with the image degradation reconstruction method based on the explicit degradation model,the proposed SG-Diffusion method achieves better reconstruction results.

Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.
Mice ; Animals ; Humans ; Glioblastoma/pathology* ; Endothelial Cells/pathology* ; DNA Copy Number Variations ; Brain/metabolism* ; Brain Neoplasms/pathology*

Objective:To explore the effect of remote gastrointestinal symptom cluster monitoring in home nutrition management of gastric cancer patients.Methods:From January to December 2021, convenience sampling was used to select 139 patients with gastric cancer undergoing adjuvant chemotherapy in the Department of Oncology Surgery and Department of Gastroenterology of Xinxiang Central Hospital as the research subject. According to the random number table method, patients were divided into a control group (69 cases) and an observation group (70 cases) . During the chemotherapy period, the control group received routine nursing, while the observation group implemented remote gastrointestinal symptom cluster monitoring for home nutrition management on the basis of the control group. The nutritional indicators, severity and distress of gastrointestinal symptom clusters, and unplanned hospitalization rates between the two groups were compared.Results:After intervention, the hemoglobin, lymphocyte count, albumin, and prealbumin in the control group were lower than those before intervention, and the Patient-Generated Subjective Global Assessment (PG-SGA) score, severity and distress scores of gastrointestinal symptom clusters were higher than those before intervention, with statistically significant differences ( P<0.05) . After intervention, the hemoglobin, lymphocyte count, albumin, and prealbumin in the observation group were higher than those in the control group, and the PG-SGA score, severity and distress of gastrointestinal symptom clusters were lower than those in the control group, with statistically significant differences ( P<0.05) . The unplanned hospitalization rates of the control group and the observation group during chemotherapy were 23.19% (16/69) and 10.00% (7/70) , respectively, with a statistically significant difference ( P<0.05) . Conclusions:Compared with routine nursing, remote gastrointestinal symptom cluster monitoring for home nutrition management can effectively stabilize the nutritional levels of gastric cancer patients during chemotherapy, alleviate gastrointestinal symptom cluster distress, and reduce unplanned hospitalization rates.

Long non-coding RNAs (lncRNAs) regulate transcription to control development and homeostasis in a variety of tissues and organs. However, their roles in the development of the cerebral cortex have not been well elucidated. Here, a bioinformatics pipeline was applied to delineate the dynamic expression and potential cis-regulating effects of mouse lncRNAs using transcriptome data from 8 embryonic time points and sub-regions of the developing cerebral cortex. We further characterized a sense lncRNA, SenZfp536, which is transcribed downstream of and partially overlaps with the protein-coding gene Zfp536. Both SenZfp536 and Zfp536 were predominantly expressed in the proliferative zone of the developing cortex. Zfp536 was cis-regulated by SenZfp536, which facilitates looping between the promoter of Zfp536 and the genomic region that transcribes SenZfp536. Surprisingly, knocking down or activating the expression of SenZfp536 increased or compromised the proliferation of cortical neural progenitor cells (NPCs), respectively. Finally, overexpressing Zfp536 in cortical NPCs reversed the enhanced proliferation of cortical NPCs caused by SenZfp536 knockdown. The study deepens our understanding of how lncRNAs regulate the propagation of cortical NPCs through cis-regulatory mechanisms.

OBJECTIVE：To provide th e ideas a nd for individualized anti-infective treatment of infection after surgery for infants and young children with intussusception and enterobrosis ，and to provide reference for clinical pharmacists participating in the clinical treatment. METHODS ：Clinical pharmacists optimized the anti-infection program for an 11-month-old infant patient infected after surgery with intussusception and enterobrosis in Ordos Central Hospital ；they put forward medication suggestions in respects of the selection of initial anti-infection treatment program ，drug replacement ，the selection of anti-infection treatment program after blood culture showed Enterococcus coli and Enterococcus faecium ，and dosage adjustment. RESULTS ：According to the judgment of the common pathogens and the hospital or community infections in the infant patient with intussusception and enterobrosis，cefoperazone sulbactam 1.0 g，q12 h was adjusted to cefoperazone sulbactam 0.5 g，q8 h combined with Metronidazole chloride sodium injection 20 mL，q8 h；when the blood culture showed E. coli （ESBL-）and E. faecium ，it was recommended to add vancomycin 0.15 g，q12 h. After poor treatment ，it was recommended to adjust the vancomycin dose to 0.2 g，q8 h. All the above suggestions were adopted by doctors. And the child ’s body temperature dropped after treatment ，the blood culture turned negative and laboratory indicators returned to normal. The child was discharged smoothly. CONCLUSIONS ：Infants and young children are special groups. Therefore ，before using antibiotics ，clinical pharmacists should evaluate the age ，body weight ，liver and kidney functions of infants and young children. They should also help doctors select and adjust drugs ，frequency and dosage on the basis of pharmacokinetic characteristics and safety ，so as to avoid adverse drug reactions while ensure curative effect.

A 4-month-old child with skin rash for 2 days and fever for 1 day was hospitalized in the Department of Pediatrics of Erdos Central Hospital in November 2019. According to the clinical symptoms, medical history and medication history at the time of admission, it was diagnosed as urticaria with angioneuroedema. In this case, the urticaria occurred 3 days after acetaminophen administration, which is a delayed reaction.