ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

The inheritance, innovation, and development of traditional Chinese medicine(TCM) need to be based on Chinese medicinal materials. The TCM seed industry is the source of TCM production, which is related to the stable supply and quality safety of TCM. This paper summarizes the basic situation of the TCM seed industry and introduces relevant policies and regulations to TCM seeds in the seed industry and the TCM field. At present, the Management Measures of TCM Seeds and Seedlings has not yet promulgated, and TCM seeds are classified as non-major crops in the category of crops for management. This paper also describes the current situation of TCM seed and seedling system construction, which is in the development stage, from six aspects, including the construction of TCM seed industry technical support system; the establishment of TCM seed standard; the construction of germplasm resource preservation system; TCM seed testing, variety registration, and variety protection; production and management of TCM seeds; TCM seed supervision. According to the development status of the TCM seed industry, four problems are put forward, including imperfect systems and standards relevant to TCM seeds, insufficient supervision and law enforcement regarding TCM seeds, insufficient policy measures and capital investment to promote the development of the industry, and the industry's falling into a low-level cycle.Accordingly, four suggestions are provided, including improving laws, regulations, and policies, perfecting standards and norms,strengthening supervision and law enforcement, and promoting support system construction, in order to boost the high-quality development of the TCM seed industry.
Seeds/chemistry* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/standards* ; Plants, Medicinal/chemistry*

Continuous manufacturing, as an innovative pharmaceutical production model, offers advantages such as high production efficiency and ease of control compared to traditional batch production, aligning with the future trend of drug production moving toward greater efficiency and intelligence. However, the development of continuous manufacturing technology in wet granulation has been slow. On one hand, this is closely related to its high technical complexity, substantial equipment investment costs, and stringent process control requirements. On the other hand, the long-term use of the traditional batch production model has created strong path dependence, and the lack of mature standardized processes further increases the difficulty of technological transformation. To promote the deep integration of wet granulation technology with continuous manufacturing, this review systematically outlines the current application of wet granulation in continuous manufacturing. It focuses on the development of key technologies such as online detection, process modeling, and process scale-up, with the aim of providing a reference for process innovation and application in wet granulation.
Drug Compounding/instrumentation* ; Technology, Pharmaceutical/methods* ; Drugs, Chinese Herbal/chemistry* ; Models, Theoretical

This paper aimed to use non-targeted urine metabolomics to reveal the potential biomarkers of toxicity in rats with hepatic injury induced by aqueous extracts of Dictamni Cortex(ADC). Forty-eight SD rats were randomly assigned to a blank group and high-dose, medium-dose, and low-dose ADC groups, with 12 rats in each group(half male and half female), and they were administered orally for four weeks. The hepatic injury in SD rats was assessed by body weight, liver weight/index, biochemical index, L-glutathione(GSH), malondialdehyde(MDA), and pathological alterations. The qPCR was utilized to determine the expression of metabolic enzymes in the liver and inflammatory factors. Differential metabolites were screened using principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA), followed by a metabolic pathway analysis. The Mantel test was performed to assess differential metabolites and abnormally expressed biochemical indexes, obtaining potential biomarkers. The high-dose ADC group showed a decrease in body weight and an increase in liver weight and index, resulting in hepatic inflammatory cell infiltration and hepatic steatosis. In addition, this group showed elevated levels of MDA, cytochrome P450(CYP) 3A1, interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α), as well as lower levels of alanine transaminase(ALT) and GSH. A total of 76 differential metabolites were screened from the blank and high-dose ADC groups, which were mainly involved in the pentose phosphate pathway, tryptophan metabolism, purine metabolism, pentose and glucuronic acid interconversion, galactose metabolism, glutathione metabolism, and other pathways. The Mantel test identified biomarkers of hepatotoxicity induced by ADC in SD rats, including glycineamideribotide, dIDP, and galactosylglycerol. In summary, ADC induced hepatotoxicity by disrupting glucose metabolism, ferroptosis, purine metabolism, and other pathways in rats, and glycineamideribotide, dIDP, and galactosylglycerol could be employed as the biomarkers of its toxicity.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Biomarkers/metabolism* ; Liver/metabolism* ; Drugs, Chinese Herbal/adverse effects* ; Female ; Chemical and Drug Induced Liver Injury/metabolism* ; Glutathione/metabolism* ; Humans

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

A nodule in the right middle lobe of the lung was treated by a combination of cone-beam CT,three-dimensional registration for fusion imaging,and electromagnetic navigation bronchoscopy-guided thermal ablation.The procedure lasted for 90 min,with no significant bleeding observed under the bronchoscope.The total radiation dose during the operation was 384 mGy.The patient recovered well postoperatively,with only a small amount of blood in the sputum and no pneumothorax or other complications.A follow-up chest CT on the first day post operation showed that the ablation area completely covered the lesion,and the patient was discharged successfully.
Humans ; Bronchoscopy/methods* ; Catheter Ablation/methods* ; Cone-Beam Computed Tomography ; Electromagnetic Phenomena ; Imaging, Three-Dimensional ; Lung Neoplasms/diagnostic imaging* ; Tomography, X-Ray Computed

The incidence of cancer is closely correlated with age,as 75％of non-small cell lung cancer(NSCLC)patients are aged at least 65 years.The availability of immune checkpoint inhibitors(ICIs)has altered the available NSCLC therapeutic pattern.Limited studies on elderly patients have demonstrated that ICIs as monotherapy provide substantial ben-efits for patients aged 65-75 years,showing no significant difference compared to younger patients.This benefit is also observed in combination with immune-combined chemotherapy or radiotherapy.For individuals older than 75 years,the survival effect was not evident,though.Immune-related adverse events(irAEs)with ICIs alone were similar in incidence across age catego-ries.Immune-combination chemotherapy resulted in a higher incidence of irAEs than chemotherapy alone,and patients &ge;75 years of age were more likely to experience higher-grade irAEs.Besides the fact that immunosenescence in older patients influ-ences the immune milieu in a multifaceted manner,which in turn impacts the effectiveness of immunotherapy,the prognosis is also influenced by the Eastern Cooperative Oncology Group performance status(ECOG PS)score,among other factors.For certain individuals aged &ge;75 years or in poor physical health,immunotherapy combined with low-intensity chemotherapy has emerged as a viable treatment option.However,there are fewer related studies,so there should be a conscious effort to increase the number of elderly patients enrolled in the trial and a comprehensive assessment to explore individualized treatment op-tions.To provide additional references and guidance for immunotherapy in elderly NSCLC patients and to propose new thera-peutic perspectives in combination with their characteristics,this review aims to summarize and analyze the pertinent studies on the application of programmed cell death protein 1(PD-1)/programmed cell death ligand 1(PD-L1)inhibitors in these patients.

Background and objective The malignant tumor that has the highest global morbidity and death rate is lung cancer,which primarily affects the elderly.The therapy landscape for non-small cell lung cancer(NSCLC)has trans-formed with the introduction of immune checkpoint inhibitors(ICIs).The purpose of this study was to compare the safety and efficacy of immune monotherapy and immunotheray combined with chemotherapy in patients with advanced NSCLC aged 75 years and above.Methods This study retrospectively analyzed 111 patients with advanced NSCLC who were at least 75 years old and received treatment at the First or Fifth Medical Centers of the People's Liberation Army General Hospital from January 2018 to October 2022.These patients underwent first-line or second-line treatment,with 70 receiving immunotherapy combined with chemotherapy and 41 receiving immunotherapy alone.Propensity score matching(PSM)was used to match the baseline characteristics of the patients,including age,Eastern Cooperative Oncology Group performance status(ECOG PS)score,and the number of treatment lines.The study endpoints included objective response rate(ORR),progression-free survival(PFS),overall survival(OS),and safety assessment.Results The median OS for the immunotherapy combined with chemother-apy group was 27.87 months,and the median PFS was 11.50 months.The median OS for the immune monotherapy group was 34.93 months,and the median PFS was 17.00 months.There were no significant differences in OS(P=0.722)and PFS(P=0.474)between the two groups,but a significant difference was observed in ORR(P=0.025).After PSM matching,each group comprised 27 patients.The median OS for the immunotherapy combined with chemotherapy group was 17.70 months,the median PFS was 8.97 months.The median OS for the immune monotherapy group was 17.87 months,and the median PFS was 11.53 months.No significant differences were observed in OS(P=0.635),PFS(P=0.878)and ORR(P=0.097).In terms of safety,the overall inci-dence of adverse events(AEs)before matching was 62.86％ in the immunotherapy combined with chemotherapy group,which was higher than 41.46％ in the immune monotherapy group(P=0.029),while there was no difference in the incidence of AEs of grade 3 or above between the two groups(P=0.221).After matching,AEs occurred in 17(62.96％ )patients in the immunotherapy combined with chemotherapy group and 13(48.15％ )in the immune monotherapy group.There were no significant differences in the overall incidence of AEs(P=0.273)or the incidence of grade 3 or above(P=0.299)between the two groups.Conclusion Im-munotherapy combined with chemotherapy does not significantly improve OS or PFS in patients with NSCLC aged 75 years and above when compared to immunotherapy alone,and this conclusion was further validated by the analysis after PSM.The safety assessment suggests that before matching,the incidence of AEs of any grade in the immunotherapy combined with chemotherapy group was higher.Still,the two groups had no difference in the incidence of AEs of grade 3 or above.Following matching,the tol-erability of the treatment was similar in both groups.According to the safety assessment,the unique circumstances and course of treatment for geriatric patients with advanced NSCLC should be considered.