Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterized by abnormal deposition of lipid in hepatocytes. If not intervened in time, NAFLD may develop into liver fibrosis or liver cancer, and ultimately threatening life. NAFLD has complicated etiology and pathogenesis, and there are no effective therapeutic means and specific drugs. Currently, insulin sensitizers, lipid-lowering agents and hepatoprotective agents are often used for clinical intervention, but these drugs have obvious side effects, and their effectiveness and safety need to be further confirmed. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in maintaining energy homeostasis. Activated AMPK can enhance lipid degradation, alleviate insulin resistance (IR), suppress oxidative stress and inflammatory response, and regulate autophagy, thereby alleviating NAFLD. Natural herbal medicines have received extensive attention recently because of their regulatory effects on AMPK and low side effects. In this article, we reviewed the biologically active natural herbal medicines (such as natural herbal medicine formulas, extracts, polysaccharides, and monomers) that reported in recent years to treat NAFLD via regulating AMPK, which can serve as a foundation for subsequent development of candidate drugs for NAFLD.

OBJECTIVE: To evaluate the safety and clinical therapeutic effect of in-line mechanical in-exsufflation to assist sputum clearance in patients with invasive mechanical ventilation. METHODS: A prospective observational study was conducted at the department of critical care medicine, the First Affiliated Hospital of Sun Yat-sen University from April 2022 to May 2023. Patients who were invasively ventilated and treated with in-line mechanical in-exsufflation to assist sputum clearance were enrolled. Baseline data were collected. Sputum viscosity, oxygenation index, parameters of ventilatory function and respiratory mechanics, clinical pulmonary infection score (CPIS) and vital signs before and after day 1, 2, 3, 5, 7 of use of the in-line mechanical in-exsufflation were assessed and recorded. Statistical analyses were performed by using generalized estimating equation (GEE). RESULTS: A total of 13 invasively ventilated patients using in-line mechanical in-exsufflation were included, all of whom were male and had respiratory failure, with the main cause being cervical spinal cord injury/high-level paraplegia (38.46%). Before the use of the in-line mechanical in-exsufflation, the proportion of patients with sputum viscosity of grade III was 38.46% (5/13) and decreased to 22.22% (2/9) 7 days after treatment with in-line mechanical in-exsufflation. With the prolonged use of the in-line mechanical in-exsufflation, the patients' CPIS scores tended to decrease significantly, with a mean decrease of 0.5 points per day (P < 0.01). Oxygenation improved significantly, with the oxygenation index (PaO₂/FiO₂) increasing by a mean of 23.3 mmHg (1 mmHg ≈ 0.133 kPa) per day and the arterial partial pressure of oxygen increasing by a mean of 12.6 mmHg per day (both P < 0.01). Compared to baseline, the respiratory mechanics of the patients improved significantly 7 days after in-line mechanical in-exsufflation use, with a significant increase in the compliance of respiratory system (Cst) [mL/cmH₂O (1 cmH₂O ≈ 0.098 kPa): 55.6 (50.0, 58.0) vs. 40.9 (37.5, 50.0), P < 0.01], and both the airway resistance and driving pressure (DP) were significantly decreased [airway resistance (cmH₂O×L^-1×s^-1): 9.6 (6.9, 10.5) vs. 12.0 (10.0, 13.0), DP (cmH₂O): 9.0 (9.0, 12.0) vs. 11.0 (10.0, 15.0), both P < 0.01]. At the same time, no new lung collapse was observed during the treatment period. No significant discomfort was reported by patients, and there were no substantial changes in heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure before and after the in-line mechanical in-exsufflation treatment. CONCLUSIONS The combined use of the in-line mechanical in-exsufflation to assist sputum clearance in patients on invasive mechanical ventilation can effectively improve sputum characteristics, oxygenation and respiratory mechanics. The in-line mechanical in-exsufflation was well tolerated by the patients, with no treatment-related adverse events, which demonstrated its effectiveness and safety.
Humans ; Prospective Studies ; Respiration, Artificial/methods* ; Respiratory Insufficiency/therapy* ; Sputum

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective To explore the hot topics and the research trend of traditional Chinese medicine treatment of chronic obstruc-tive pulmonary disease in 2017-2021,and to aware the cooperation among authors and institutions in the field.Methods Literature on TCM treatment of chronic obstructive pulmonary disease published in CNKI and PubMed in 2017-2021 was searched,and CiteSpace 5.8 R3 was used to visualize the authors,research institutions and keywords of the included literatures.Results A total of 3082 Chinese literatures and 1093 English literatures were included.In 2017-2021,the trend of publication has always shown a steady growth,and there was a lack of communication and cooperation among authors and teams.Keywords visualization map showed 18 clusters and 20 emer-gent words.Conclusion Traditional Chinese medicine treatment of chronic obstructive pulmonary disease is mainly focused on syndrome type,treatment methods,disease mechanism and related curative effect indicators,and the syndrome differentiation analysis and clinical curative effect evaluation of traditional Chinese medicine compounds are still the main forces at present.As the patients quality of life is becoming more and more attention,how to strengthen pulmonary rehabilitation education,improve patient compliance,and expand the lo-cation and area of pulmonary rehabilitation is one of the current research trends.

Objective:To evaluate the clinical efficacy, tolerability and safety of adjunctive perampanel in focal epilepsy patients≥12 years old.Methods:One hundred and nineteen focal epilepsy patients≥12 years old accepted adjunctive perampanel in Department of Neurology, First Affiliated Hospital of Guangxi Medical University from July 2020 to December 2022 were chosen. At 1-3 months, 4-6 months, 7-9 months and 10-12 months after adjunctive perampanel, seizure frequency changes every 28 d, medication retention rate and adverse reactions were recorded to evaluate the clinical efficacy (a reduction in seizure frequency≥50% from baseline was defined as overall valid treatment), tolerability and safety of adjunctive perampanel. According to efficacy results after adjunctive perampanel of 4-6 months (short-term) and 10-12 months (long-term), these patients were divided into valid group and invalid group; and the influencing factors for short-term and long-term efficacy were analyzed.Results:At 1-3, 4-6, 7-9, 10-12 months after adjunctive perampanel, reduction in seizure frequency every 28 d was 66.7% (24.3%, 97.2%), 77.5% (48.6%, 100%), 94.6% (50%, 100%), 100% (70.9%, 100%), enjoying overall valid rate of 60.2% (59/98), 75.0% (7/76), 78.9% (45/57), 86.5% (32/37). The retention rate at 3, 6, 9 and 12 months after adjunctive perampanel was 85.2% (98/115), 67.9% (76/112), 54.3% (57/105), 41.1% (37/90). Adverse reactions were reported in 33 patents (27.7%), mainly with dizziness and secondly with mental symptoms. After short-term and long-term adjunctive perampanel, no significant difference was noted in gender, initial age of adjunctive perampanel, course of disease, etiology, EEG results, imaging results, number and type of combined anti-seizure drugs, or maximum dose of pirampanel between the valid group and invalid group ( P>0.05). Conclusion:Perampanel has good efficacy, tolerability and safety in adolescents and adults≥12 years old with focal epilepsy; no clear influencing factors for pirampanel valid treatment is found so far.

Objective To investigate the effects of long-term administration of tacrolimus(also known as FK506)on the pain-related behaviors in mice and to study the underlying mechanism of pain induced by FK506 via measuring the effect of FK506 on the synaptic expression and phosphorylation of alpha-amino-3-hyroxy-5-methyl-4-isoxazolepropionic acid(AMPA)receptor in the spinal cord dorsal horn of mice.Methods 1)A total of 24 mice were evenly and randomly assigned to two groups,a FK506 group and a Saline group.The FK506 group was given daily intraperitoneal injection of FK506 and the Saline group received normal saline.Both groups received injection once a day for 7 days in a row.Some of the mice(n=6 in each group)were monitored for the changes in the paw withdrawal threshold(PWT),the paw withdrawal latency(PWL),and the spontaneous pain behaviors to establish the pain model.The other mice(n=6 in each group)of each group underwent isolation of the dorsal horn when obvious pain symptoms were induced on day 7 of injection.Then,immunoblotting was performed to determine the synaptic expression and phosphorylation levels of GluA1 and GluA2 subunits of AMPA receptors.2)The mice were randomly divided into two groups,FK506+calcineurin(CaN)group and FK506+Saline group(n=6 in each group).After the pain model was constructed,the mice were given intrathecal injection of recombinant CaN(also know as 33 U)or normal saline.Then,60 minutes later,the PWT and the PWL of the mice were measured to investigate the role of CaN in FK506-induced pain.3)Another18 mice were selected.The mice were randomly and evenly assigned to three groups,a control group(receiving intraperitoneal injection of normal saline followed by intrathecal injection of normal saline),FK506+Saline group(receiving intraperitoneal injection of FK506 followed by intrathecal injection of normal saline)and FK506+CaN group(receiving intraperitoneal injection of FK506 followed by intrathecal injection of CaN).Then,60 minutes later,the spinal cords were isolated and subjected to immunoblotting assay to determine the role of CaN in FK506-induced AMPA receptor modification.Results 1)After 7 consecutive days of intraperitoneal injection of FK506,the PWT and PWL of mice dropped significantly,reaching on day 7 as low as 22.3%±0.05%and 66.6%±0.05%of the control group,respectively(P<0.01).The FK506-treated mice displayed evident spontaneous pain behavior,presenting significantly increased licking activities(P<0.01).These results indicated that FK506-induced pain model was successfully established.Immunoblotting assay showed that the total expressions of GluA1 and GluA2 subunits in the spinal dorsal horn of the FK506 group remained unchanged in comparison with those of the Saline group.However,FK506 specifically induced an increase in the synaptic expression of GluA1.In addition,the phosphorylation levels of GluA1 at Ser845 and Ser831 in FK506-treated mice were significantly increased in comparison with those of the control group(P<0.05).2)Compared with those of the mice in the FK506+Saline group,the PWT and the PWL of mice in the FK506+CaN group were significantly increased(P<0.05).3)Compared with those of the FK506+Saline group,the synaptic expression of GluA1 were decreased in FK506+CaN group(P<0.01)and the phosphorylation levels of GluA1 at Ser845 and Ser831 were significantly downregulated(P<0.001).Conclusion The hyper-expression and hyperphosphorylation of GluA1 subunit in the spinal cord dorsal horn resulting from CaN inhibition contributes to the FK506-induced pain syndrome.FK506 induces the synaptic hyper-expression and hyperphosphorylation of GluA1 in the dorsal horn of the spinal cord through CaN inhibition,thereby inducing pain.

ObjectiveTo investigate the clinical feature peripheral neuropathy and vasculopathy after acrylamide toxication. Methods2 young male patients with peripheral neuropathy who had exposed to acrylamide for job more than one year were reported.ResultsNeuroelectrophysiological examination showed marked abnormalities in both peripheral and central nerve conduction in both patients. Sural nerve biopsies revealed axonal degeneration, Wallerian degeneration and giant axon with accumulated neurofilaments. Additonally, vasculopathies including prominant thickness of arterial intesma and basal membrane of capillary as well as apoptosis of vascular pericyte, were evident. ConclusionAxonal degeneration and vascular involvement has been found in acrylamide toxication. Vascular impairment maybe plays an important role in the pathogenesis of neuropathy.