BACKGROUND:Lysosomal storage diseases,as a group of rare genetic metabolic disorders,exhibit complex pathogenesis often leading to dysfunction of cells,tissues,and organs.Current therapeutic approaches have certain limitations.Stem cell transplantation,as an emerging treatment method,offers new options for patients with lysosomal storage diseases.OBJECTIVE:To review the mechanisms of action of stem cells in regulating lysosomes for the treatment of lysosomal storage diseases and explore the feasibility of traditional Chinese medicine in treating such diseases,providing new insights for the treatment of lysosomal storage diseases with stem cells.METHODS:Relevant literature from 2010 to 2024 was searched in CNKI and PubMed databases using keywords"stem cells,lysosomal storage disease,lysosome"in English and Chinese.Ultimately,78 articles were included for review and analysis.RESULTS AND CONCLUSION:(1)Stem cells treat lysosomal storage diseases by regulating lysosomes primarily through three aspects:regulating stem cell differentiation and replacement,improving intercellular communication and the microenvironment,and enhancing lysosomal enzyme expression through gene editing.(2)Stem cells have achieved significant effects in the treatment of some lysosomal storage diseases,such as Niemann-Pick disease,mucopolysaccharidoses,Gaucher disease,and metachromatic leukodystrophy.(3)The procedure for stem cell transplantation needs further optimization.Adverse reactions post-transplantation urgently need to be addressed,and the efficiency and safety of gene-modified stem cells also need to be further improved.In the future,more research on the treatment of lysosomal storage diseases with traditional Chinese medicine is required to reveal the relevant mechanisms for the treatment of lysosomal storage diseases with traditional Chinese medicine.

BACKGROUND:Lysosomal storage diseases,as a group of rare genetic metabolic disorders,exhibit complex pathogenesis often leading to dysfunction of cells,tissues,and organs.Current therapeutic approaches have certain limitations.Stem cell transplantation,as an emerging treatment method,offers new options for patients with lysosomal storage diseases.OBJECTIVE:To review the mechanisms of action of stem cells in regulating lysosomes for the treatment of lysosomal storage diseases and explore the feasibility of traditional Chinese medicine in treating such diseases,providing new insights for the treatment of lysosomal storage diseases with stem cells.METHODS:Relevant literature from 2010 to 2024 was searched in CNKI and PubMed databases using keywords"stem cells,lysosomal storage disease,lysosome"in English and Chinese.Ultimately,78 articles were included for review and analysis.RESULTS AND CONCLUSION:(1)Stem cells treat lysosomal storage diseases by regulating lysosomes primarily through three aspects:regulating stem cell differentiation and replacement,improving intercellular communication and the microenvironment,and enhancing lysosomal enzyme expression through gene editing.(2)Stem cells have achieved significant effects in the treatment of some lysosomal storage diseases,such as Niemann-Pick disease,mucopolysaccharidoses,Gaucher disease,and metachromatic leukodystrophy.(3)The procedure for stem cell transplantation needs further optimization.Adverse reactions post-transplantation urgently need to be addressed,and the efficiency and safety of gene-modified stem cells also need to be further improved.In the future,more research on the treatment of lysosomal storage diseases with traditional Chinese medicine is required to reveal the relevant mechanisms for the treatment of lysosomal storage diseases with traditional Chinese medicine.

Ischemic stroke （IS） is an acute cerebrovascular disease caused by insufficient blood supply to the brain， resulting in brain tissue necrosis and neurological dysfunction. It is characterized by impaired motor， language， sensory， cognitive， and other functions. The pathogenesis involves inflammatory responses， excitotoxicity of excitatory amino acids， and mitochondrial dysfunction. IS with a high incidence， high mortality， high disability， and a high recurrence rate is the leading cause of death in China. At present， Western medical therapies mainly focus on vascular recanalization， including thrombolysis and mechanical thrombectomy. However， due to the possibility of cerebral hemorrhage and edema， narrow time windows， and contraindications associated with intravascular therapy， only a few patients can benefit from these therapies， which greatly limit their clinical application. IS belongs to the categories such as stroke， hem iplegia， and major syncope in traditional Chinese medicine （TCM）. It is mainly caused caused by wind， fire， phlegm， and stasis， which lead to imbalance of Yin and Yang， disorder of Qi and blood， and invasion of clear orifices. The common treatment methods include calming the liver and dispelling wind， resolving phlegm and unblocking meridians， and activating blood and resolving stasis. TCM acting on multiple pathways and targets with low toxicity and side effects has definite effects in improving the prognosis and reducing the recurrence rate， being worthy of promotion and research. Brain-derived neurotrophic factor （BDNF） plays a key role in promoting neurogenesis and increasing synaptic plasticity. During the progression of IS， BDNF binds to tyrosine kinase receptor B （TrkB） to initiate intracellular signaling cascades， thus exerting neuroprotective effects. Studies have shown that TCM can regulate the BDNF/TrkB signaling pathway， treating IS by regulating synaptic plasticity and promoting neural repair. This paper summarizes and generalizes the mechanisms of active components， single herbs， and compound prescriptions of TCM in regulating the BDNF/TrkB signaling pathway in the treatment of IS through the review of domestic and foreign literature in recent years， aiming to provide a theoretical basis and treatment reference for the treatment of IS with TCM.

Objective The molding process of compound Shexiang Huangqi dropping pills was optimized by central composite design and response surface method,the determination of volatile components in the compound by gas chromatography was established in order to improve the quality standard of the compound.Methods Single factor method was used to select the optimum range of matrix type,the ratio of matrix to liquid,and drop distance of compound Shexiang Huangqi dropping pills;Appearance traits,a difference of pill weight,and dissolution time were used as evaluation indexes,the optimum forming process conditions of compound Shexiang Huangqi dropping pills were optimized by central composite design and response surface method;Three batches of compound Shexiang Huangqi dropping pills were taken as test samples and determined by gas chromatography;The gas chromatographic column was HP-5 sillica capillary column,the inlet temperature was 260 ℃,the temperature was programmed,and the detector temperature was 300 ℃,the split ratio was 10∶1,nitrogen was selected as the carrier gas with a flow rate of 1.0 mL·min-1.Results The optimum forming process conditions of compound Shexiang Huangqi dropping pills were selected by central composite design and response surface method as a matrix:matrix=0.99,drug:matrix=0.55,drop distance=6.00,and the comprehensive score were 0.845 2.Under these conditions,the quality of the prepared dropping pills was the best;The chromatographic peaks of borneol,muscone,and ligustilide reached the baseline separation;the linear ranges of the three components were 0.327-1.962,0.140-0.840,0.710 5-4.263 μg(all r＞0.999);The average recoveries were 92.30％(RSD=1.65％,n=6),101.28％(RSD=0.81％,n=6)and 98.99％(RSD=0.65％,n=6);The average contents of the three components were 0.201 7,0.084 7 and 1.382 9 mg·g-1,respectively.Conclusions The forming process is stable and feasible,which can provide a reference for the development and application of compound Shexiang Huangqi dropping pills;The gas chromatography method established can simultaneously determine the contents of borneol,muscone,and ligustilide in compound Shexiang Huangqi dropping pills,which can be used for quality control of compound Shexiang Huangqi dropping pills.

Objective The molding process of compound Shexiang Huangqi dropping pills was optimized by central composite design and response surface method,the determination of volatile components in the compound by gas chromatography was established in order to improve the quality standard of the compound.Methods Single factor method was used to select the optimum range of matrix type,the ratio of matrix to liquid,and drop distance of compound Shexiang Huangqi dropping pills;Appearance traits,a difference of pill weight,and dissolution time were used as evaluation indexes,the optimum forming process conditions of compound Shexiang Huangqi dropping pills were optimized by central composite design and response surface method;Three batches of compound Shexiang Huangqi dropping pills were taken as test samples and determined by gas chromatography;The gas chromatographic column was HP-5 sillica capillary column,the inlet temperature was 260 ℃,the temperature was programmed,and the detector temperature was 300 ℃,the split ratio was 10∶1,nitrogen was selected as the carrier gas with a flow rate of 1.0 mL·min-1.Results The optimum forming process conditions of compound Shexiang Huangqi dropping pills were selected by central composite design and response surface method as a matrix:matrix=0.99,drug:matrix=0.55,drop distance=6.00,and the comprehensive score were 0.845 2.Under these conditions,the quality of the prepared dropping pills was the best;The chromatographic peaks of borneol,muscone,and ligustilide reached the baseline separation;the linear ranges of the three components were 0.327-1.962,0.140-0.840,0.710 5-4.263 μg(all r＞0.999);The average recoveries were 92.30％(RSD=1.65％,n=6),101.28％(RSD=0.81％,n=6)and 98.99％(RSD=0.65％,n=6);The average contents of the three components were 0.201 7,0.084 7 and 1.382 9 mg·g-1,respectively.Conclusions The forming process is stable and feasible,which can provide a reference for the development and application of compound Shexiang Huangqi dropping pills;The gas chromatography method established can simultaneously determine the contents of borneol,muscone,and ligustilide in compound Shexiang Huangqi dropping pills,which can be used for quality control of compound Shexiang Huangqi dropping pills.

OBJECTIVE To identify tortoiseshell glue and antler glue in Qichong zuogui granules,and determine the contents of 12 chemical components.METHODS Identification and content determination were performed by using liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The identification was performed on Hypersil GOLD column with a mobile phase consisted of acetonitrile-0.1％formic acid solution(gradient elution);the electrospray ion source was used to scan in the positive ion multi-reaction detection mode.The mass charge ratio(m/z)631.3→546.4,631.3→921.4 was the detection ion pair for tortoiseshell glue,and the m/z 765.4→554.0,765.4→733.0 was the detection ion pair for antler glue.The determination method for 12 chemical components was as follows:Accucore C18 column,methanol-0.1％formic acid as mobile phase(gradient elution);scanning range of positive and negative ions was m/z 100→1 000 with the electric spray ion source and single ion detection scanning mode.RESULTS Average retention times of the molecular ion peaks for characteristic peptide segments of tortoiseshell glue and antler glue were 6.28 and 6.77 min,respectively;the linear relationship of 12 chemical components was good within their respective concentration ranges,such as astragaloside Ⅳ,calycosin-7-O-β-D-glucoside,calycosin,chlorogenic acid,ferulic acid,betaine,amygdalin,rutin,hydroxysafflor yellow A,hyperoside,loganin,cyasterone(r＞0.999);RSDs for precision,stability(24 h)and reproducibility tests were all less than 5％.The average sample recovery rates ranged from 98.04％to 101.08％.The average contents of 12 components were 1.83,25.73,13.76,56.71,23.80,49.82,807.49,15.01,317.02,60.21,202.71 and 17.70 μg/g,respectively.CONCLUSIONS In this study,tortoiseshell glue and antler glue in Qixiong zuogui granules are identified,and the contents of 12 chemical components therein are determined.This provides a reference for the quality control of this granule.

BACKGROUND:Studies have shown that mitochondrial apoptosis of alveolar epithelial cells plays an important role in the pathogenesis of pulmonary fibrosis,and Feibi prescription can attenuate pulmonary fibrosis and inhibit the transformation of extracellular mechanisms in mice with pulmonary fibrosis. OBJECTIVE:To investigate the mechanism of Feibi prescription on mitochondrial apoptpsis of alveolar epithelial cells in bleomycin induced pulmonary fibrosis mice. METHODS:Forty male C57BL/6 mice were randomly divided into blank control group,model group,pirfenidone group,and Feibi prescription group.There were 10 mice in each group.Except for the blank control group,the other three groups were intraperitoneally injected with bleomycin(7.5 mg/kg per day)for 10 continuous days to establish the model of pulmonary fibrosis.On day 1 after modeling,the mice in corresponding drug groups were intragastrically administered with pirfenidone(51.43 mg/kg per day)or Feibi prescription(12.86 mg/kg per day).Drug administration lasted for 28 days.Then,morphological changes of lung tissue in mice were observed by hematoxylin-eosin staining and Masson staining.The levels of interleukin-1,interleukin-6,interleukin-17,and interleukin-37 in the serum were detected by ELISA,and the expression of Bax,Bcl-2,Beclin-1,and Caspase3 in the lung tissue was detected by western blot assay. RESULTS AND CONCLUSION:Morphological observation of lung tissue showed that in the model group,the alveolar septum and alveolar lumen were infiltrated with a large number of inflammatory cells,and there were large clusters of fibrous foci;in the pirfenidone group,alveolar septa were thickened,with a small infiltration of inflammatory cells and the appearance of pulmonary fibrous foci;in the Feibi prescription group,the alveolar structure was widened,with a small amount of inflammatory cell infiltration,and the alveolar structure was almost not obviously damaged,with a small number of lung fibrous foci.Compared with the blank control group,the mass concentrations of interleukin-1,interleukin-6,interleukin-17,and interleukin-37 were significantly higher in the model group(P<0.01),while the levels were significantly lower in the two drug groups than the model group(P<0.01).Moreover,the mass concentrations of interleukin-1,interleukin-6,interleukin-17,and interleukin-37 in the Feibi prescription group were lower than those in the pirfenidone group.Compared with the blank control group,the expression of Bax and Caspase3 proteins in the lung tissue of mice was significantly higher in the model group,while the expression of Bax and Caspase3 proteins was significantly lower in the two drug groups than the model group.Compared with the blank control group,the expression of Bcl-2 and Beclin-1 proteins in the lung tissue of mice was significantly lower in the model group,while the expression of Bcl-2 and Beclin-1 proteins was significantly higher in the two drug groups than the model group.To conclude,Feibi prescription can reduce pulmonary fibrosis and its mechanism may be related to the downregulation of interleukin-1,interleukin-6,interleukin-17,and interleukin-37 levels.This prescription can also reduce the apoptosis of alveolar epithelial cells by regulating mitochondrial apoptosis-related proteins,Bax,Bcl-2,Beclin-1 and Caspase3.

Nigella sativa L. seeds have been traditionally utilized in Chinese folk medicine for centuries to treat vitiligo. This study revealed that the ethanolic extract of Nigella sativa L. (HZC) enhances melanogenesis and mitigates oxidative stress-induced cellular senescence and dysfunction in melanocytes. In accordance with established protocols, the ethanol fraction from Nigella sativa L. seeds was extracted, concentrated, and lyophilized to evaluate its herbal effects via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, tyrosinase activity evaluation, measurement of cellular melanin contents, scratch assays, senescence-associated β-galactosidase (SA-β-gal) staining, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis for expression profiling of experimentally relevant proteins. The results indicated that HZC significantly enhanced tyrosinase activity and melanin content while notably increasing the protein expression levels of Tyr, Mitf, and gp100 in B16F10 cells. Furthermore, HZC effectively mitigated oxidative stress-induced cellular senescence, improved melanocyte condition, and rectified various functional impairments associated with melanocyte dysfunction. These findings suggest that HZC increases melanin synthesis in melanocytes through the activation of the MAPK, PKA, and Wnt signaling pathways. In addition, HZC attenuates oxidative damage induced by H₂O₂ therapy by activating the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and enhancing the activity of downstream antioxidant enzymes, thus preventing premature senescence and dysfunction in melanocytes.
Oxidative Stress/drug effects* ; Melanocytes/cytology* ; Cellular Senescence/drug effects* ; Nigella sativa/chemistry* ; Plant Extracts/pharmacology* ; Seeds/chemistry* ; Mice ; Animals ; Melanins/metabolism* ; Monophenol Monooxygenase/metabolism* ; Humans

As an airway management tool,the seal performance of the laryngeal mask is crucial.The seal pressure of the laryngeal mask is a key indicator for evaluating the performance of the laryngeal mask.Appropriate seal pres-sure is of great clinical significance to ensure effective ventilation and avoid complications.This article reviews the factors that affect the seal pressure of the laryngeal mask,including structural design,material characteristics,in-flation volume,insertion skill,airway pressure,and patients'individual characteristics.Understanding and optimi-zing the above factors can help anesthesiologists to better apply the laryngeal mask in clinical anesthesia,to reduce patient complications,and improve patient safety as well as comfort.

Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.