Background Pneumoconiosis is a chronic inflammatory disease that cannot be completely cured. Therefore, how to control lung inflammation and delay of the body aging is one of the keys to treating pneumoconiosis. The studies in past two decades suggested that many small molecule drugs are able to enhance cardiopulmonary function. Objective To explore the effects of homeopathic dosing and combined dosing of β-nicotinamide mononucleotide and taurine on experimental silicosis in rats. Methods Seventy-two SD specific pathogen-free rats were randomized into 4 groups (18 mice in each group): negative control group (ultrapure water, without dust), positive control group, homeopathic treatment group, co-administered treatment group. One mL of quartz dust suspension was injected into the rat trachea by disposable non-exposed tracheal injection method (50 mg·mL⁻¹) to establish a rat silicosis model. Rats were administered by gavage since the 4th day after dust exposure. The homeopathic treatment group rats received taurine solution (0.03 g·mL⁻¹) in the morning and β-nicotinamide mononucleotide (0.03 g·mL⁻¹) in the afternoon; the co-administered treatment group rats received a mixed solution (0.015 g·mL⁻¹ β-nicotinamide mononucleotide + 0.015 g·mL⁻¹ taurine) twice, in the morning and afternoon respectively. The positive and negative control groups received equivalent of ultrapure water in the morning and afternoon. All groups of rats were administered 5 d a week for a total of 6 weeks. The rats were neutralized after 6 weeks of administration. Organ coefficient, lung hydroxyproline content, whole lung dry and wet weights, whole lung free silica content, and cell count and classification in lung lavage fluid were measured and calculated, and lung histopathological changes in lung samples were observed. Results Compared with the positive control group, the whole lung wet weight, whole lung dry weight , total cell count, neutrophil rate, lung organ coefficient, lung hydroxyproline content, and whole lung free silica content were reduce in the homeopathic treatment group, and the co-administered treatment group (P＜0.05). Compared with the negative control group, the total cell count, neutrophil rate, lung organ coefficient, lung hydroxyproline content, and whole lung free silica content were elevated in the homeopathic treatment group and the co-administered treatment group, the whole lung dry weight was elevated in the co-administered treatment group, and those differences were all statistically significant (P＜0.05). The rat lung histopathological results showed that, in the positive control group, round or oval nodules were formed in the lung tissue, which were phagocytic cellular nodules, and the alveolar structures in some areas still existed. The histopathological changes in the homeopathic treatment group and the co-administered treatment group were similar to those of the positive group, but less severe. No pathological change was observed in the lung tissue of the negative control group. Conclusion Some improvement and dust removal in experimental silicosis rats by homeopathic dosing and combined dosing of β-nicotinamide mononucleotide and taurine are observed.

Cervical cancer is one of the most common gynecological malignant tumors in China. Given their lack of obviously early symptoms, more than half of patients with cervical cancer are diagnosed in the middle and late stages of this malignancy, resulting in poor prognosis. Finding new therapeutic targets is the current research direction. Metabolomics, as a new omics technology, is expected to provide new targets for tumor precision diagnosis and treatment through the analysis of the changes and potential mechanisms of metabolites in tumor occurrence and development by chromatography, mass spectrometry, and other technologies. Herein, we review the research methods of metabolomics; metabolic characteristics of cervical cancer; and progress of the research on metabolomics in cervical cancer diagnosis, curative effect prediction, and prognosis evaluation to provide new ideas for the precise diagnosis and treatment of cervical cancer.

Social behavior is extremely important for the physical and mental health of individuals, their growth and development, and for social development. Social behavioral disorders have become a typical clinical representation of a variety of psychiatric disorders and have serious adverse effects on the development of individuals. The prefrontal cortex, as one of the key areas responsible for social behavior, involves in many advanced brain functions such as social behavior, emotion, and decision-making. The neural activity of prefrontal cortex has a major impact on the performance of social behavior. Numerous studies demonstrate that neurons and glial cells can regulate certain social behaviors by themselves or the interaction which we called neural microcircuits; and the collaboration with other brain regions also regulates different types of social behaviors. The prefrontal cortex (PFC)-thalamus projections mainly influence social dominance and social preference; the PFC-amygdala projections play a key role in fear behavior, emotional behavior, social exploration, and social identification; and the PFC-nucleus accumbens projections mainly involve social preference, social memory, social cognition, and spatial-social associative learning. Based on the above neural mechanism, many studies have focused on applying the non-invasive neurostimulation to social deficit-related symptoms, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES) and focused ultrasound stimulation (FUS). Our previous study also investigated that repetitive transcranial magnetic stimulation can improve the social behavior of mice and low-intensity focused ultrasound ameliorated the social avoidance behavior of mice by enhancing neuronal activity in the prefrontal cortex. In this review, we summarize the relationship between neurons, glial cells, brain projection and social behavior in the prefrontal cortex, and systematically show the role of the prefrontal cortex in the regulation of social behavior. We hope our summarization will provide a reference for the neural mechanism and effective treatment of social disorders.

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.

Head and neck squamous cell carcinoma(HNSCC)is characterized by high recurrence or distant metastases rate and the prognosis is challenging.There is mounting evidence that tumor-infiltrating B cells(TIL-Bs)have a crucial,synergistic role in tumor control.However,little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade.Using single-cell RNA sequencing(scRNA-seq)data from the Gene Expression Omnibus(GEO)database,the study identified distinct gene expression patterns in TIL-Bs.HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering.This classification was further validated with TCGA HNSCC data,correlating with patient prognosis,immune cell infiltration,and response to immunotherapy.We found that the B cells activation group exhibited a better prognosis,higher immune cell infiltration,and distinct immune checkpoint levels,including elevated PD-L1.A prognostic model was also developed and validated,highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients.Overall,this study provides a foundational approach for B cells-based tumor classification in HNSCC,offering insights into targeted treatment and immunotherapy strategies.

Dwarfism is a globally rare growth disorder,usually caused by genetics or disease,with the most prominent phenotype being short stature.Animal models are important tools for studying its pathogenesis,prevention,and treatment options,and identifying potential therapeutic targets and biomarkers.The development of genetic engineering technology has greatly promoted the application of gene-edited animal models in the study of dwarfism.In this review,we summarize and discuss the existing animal models of dwarfism in terms of their theoretical basis,model characteristics,and research applications.This offers a reference for researchers and clinicians aiming to better conduct research on the pathogenesis and prevention of dwarfism.

Aim To investigate the regulation of death-associated protein kinase 1(DAPK1)on seizure-in-duced Alzheimer's disease(AD)-like pathology.Methods Two-month old C57BL/6 mice were given intraperitoneal injection of 25 mg·kg-1 kainic acid(KA)to establish a temporal lobe epilepsy(TLE)model,and control mice were injected with an equal a-mount of saline.The expression of key proteins in the amyloid metabolic pathway,the secretion of soluble am-yloid β-protein(Aβ),the high phosphorylation of tau,and the activation of DAPK1 pathway were detected in hippocampus of mice.WT mice and Dapk1 KO mice were given intraperitoneal injections of KA,then the effect of DAPK1 on seizure-induced AD-like pathology was examined.Results The secretion of soluble Aβ,the expression of key proteins in the amyloid metabolic pathway,the level of phosphorylation of tau,and the ex-pression and activity of DAPK1 were higher in the hip-pocampus of TLE mice than in the control mice.Com-pared with WT mice,KA-induced Aβ secretion and tau phosphorylation were significantly reduced in hippo-campus of Dapk1 KO mice.Conclusion TLE in-duces AD-like pathology in mice,and DAPK1 knockout alleviates symptoms of aging in mouse brain.

Pleomorphic adenoma (PA) is the most common benign tumour in the salivary gland and has high morphological complexity. However, the origin and intratumoral heterogeneity of PA are largely unknown. Here, we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations, three recapitulating the epithelial states of the normal parotid gland, and two PA-specific epithelial cell (PASE) populations unique to tumours. Then, six subgroups of PASE cells were identified, which varied in epithelium, bone, immune, metabolism, stemness and cell cycle signatures. Moreover, we revealed that CD36⁺ myoepithelial cells were the tumour-initiating cells (TICs) in PA, and were dominated by the PI3K-AKT pathway. Targeting the PI3K-AKT pathway significantly inhibited CD36⁺ myoepithelial cell-derived tumour spheres and the growth of PA organoids. Our results provide new insights into the diversity and origin of PA, offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.
Humans ; Adenoma, Pleomorphic/genetics* ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Transcriptome ; Myoepithelioma

OBJECTIVE: To observe the effects of the Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on hemorrhagic transformation and limb motor function after intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in stroke patients. METHODS: A total of 130 stroke patients after rt-PA thrombolytic were divided into an acupuncture group (58 cases, 1 case dropped off) and a non-acupuncture group (72 cases, 7 cases dropped off) according to whether they received acupuncture treatment. Propensity score matching (PSM) was used to match each group, with 38 patients in each group. The patients in the non-acupuncture group received rt-PA thrombolytic therapy and western medical basic treatment. In addition to the basic treatment, the patients in the acupuncture group received Xingnao Kaiqiao acupuncture at Shuigou (GV 26), bilateral Neiguan (PC 6), and ipsilateral Sanyinjiao (SP 6), Chize (LU 5), once a day for 14 days. The incidence of hemorrhagic transformation within 30 days after onset was compared between the two groups. The Fugl-Meyer assessment (FMA) score and activities of daily living (ADL) score were observed at baseline and 30 days, 6 months, 1 year after onset in the two groups. The disability rate at 6 months and 1 year after onset was recorded, and safety was evaluated in both groups. RESULTS: The incidence of hemorrhagic transformation in the acupuncture group was 5.3% (2/38), which was lower than 21.1% (8/38) in the non-acupuncture group (P<0.05). At 30 days, 6 month, and 1 year after onset, the FMA and ADL scores of both groups were higher than those at baseline (P<0.01), and the scores in the acupuncture group were higher than those in the non-acupuncture group (P<0.01). The disability rate in the acupuncture group at 1 year after onset was 10.5% (4/38), which was lower than 28.9% (11/38) in the non-acupuncture group (P<0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05). CONCLUSION The Xingnao Kaiqiao acupuncture method could reduce the incidence of hemorrhagic transformation in stroke patients after intravenous thrombolysis with rt-PA, improve their motor function and daily living ability, and reduce the long-term disability rate.
Humans ; Tissue Plasminogen Activator/adverse effects* ; Activities of Daily Living ; Prospective Studies ; Stroke ; Acupuncture Therapy ; Thrombolytic Therapy/adverse effects*

Objective: To analyze the follow-up and clinical effect of multidisciplinary treatment on the children with spinal muscular atrophy (SMA). Methods: The clinical data including nutritional status, respiratory function, bone health and motor function of 45 children with SMA who received multidisciplinary management 1-year follow-up in the Children's Hospital, Zhejiang University School of Medicine from July 2019 to October 2021 were retrospectively collected. Comparisons before and after management were performed using paired-samples t-test or Wilcoxon rank-sum test, etc. Results: The age of 45 patients (25 boys and 20 girls) was 50.4 (33.6, 84.0) months at the enrollment, with 6 cases of type 1, 22 cases of type 2, and 17 cases of type 3 respectively. After the multidisciplinary management, the cases of SMA patients with malnutrition decreased from 22 to 12 (P=0.030), the level of vitamin D were significantly increased ((45±17) vs. (48±14) nmol/L, t=-4.13, P<0.001). There was no significant difference in the forced vital capacity %pred, the forced expiratory volume at 1 second %pred, and the peak expiratory flow %pred ((76±19)% and (76±21)%, (81±18)% and (79±18)%, (81±21)% and (78±17)%; t=-0.24, 1.36, 1.21; all P>0.05). The Cobbs angle of scoliosis also improved significantly (8.0°(0°, 13.0°) vs. 10.0°(0°, 18.5°), Z=-3.01, P=0.003). The Hammersmith functional motor scale expanded scores of children with SMA type 2 and type 3 both showed significant elevation (11.0 (8.0, 18.0) vs. 11.0 (5.0, 18.5) scores, 44.0 (36.5, 53.0) vs. 44.0 (34.0, 51.5) scores, Z=2.44, 3.11, P=0.015, 0.002). Conclusion: Multidisciplinary management is beneficial for delaying the progression of the multi-system impairments of SMA patients, such as malnutrition, restrictive ventilation dysfunction and scoliosis.
Child ; Male ; Female ; Humans ; Child, Preschool ; Scoliosis ; Retrospective Studies ; Follow-Up Studies ; Muscular Atrophy, Spinal ; Malnutrition