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.

Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR –/–mice given high-fat diet to investigate the effects of monotropein on atherosclerosis.Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.

Objective To investigate the effects of chronic restraint stress for 28 days(day and night)on mood and cognitive-like behavior in male and female ICR mice,to provide a basis for the selection of sex and restraint period in chronic restraint stress model animals.Methods A total of 72 male and female(1∶1)ICR mice were divided into six groups:male control,daytime restraint,and nighttime restraint groups,and female control,daytime restraint,and nighttime restraint groups.Mice in all but the control groups were bound for 10 h/d and restrained continuously for 28 days to establish a chronic restraint stress model.The emotional and cognitive behaviors induced by restraint in male and female mice at different times were observed by open field,Y maze,novel inhibition feeding,elevated cross maze,tail suspension,forced swimming,and dark-avoidance experiments.Results In the tail suspension experiment,the immobility time of male mice in the daytime restraint group was significantly increased compared with that in the control group(P＜0.05),and the immobility times of male mice in the daytime and nighttime restraint groups were also significantly increased in the forced swimming experiment,compared with those in the control group(P＜0.05).There was no significant difference between the female daytime restraint and female control groups in the novelty inhibition feeding experiment,but the feeding latency of the nighttime restraint group was significantly longer than that of the control group(P＜0.05)and the daytime restraint group(P＜0.05).The feeding latency of female mice was significantly longer than that of males during nighttime restraint(P＜0.05).In the open field test,compared with the male control group,the female control group showed a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).Compared with the female control group,the female daytime restraint group exhibited a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).There was no significant difference between the groups in the elevated cross maze and Y maze experiments.There was no significant difference in dark latency between the daytime restraint group and the control group,but darkness latency was significantly shorter in the nighttime restraint group compared with those in the control group(P＜0.05).When male and female mice were combined,the immobility time in the daytime restraint group was significantly increased in the tail suspension experiment(P＜0.05),the immobility times of mice in the daytime and nighttime restraint groups were significantly increased in the forced swimming experiment(P＜0.01,P＜0.05),and the central zone time and the ratio of central area time to peripheral area time of daytime restraint mice were significantly shorter compared with those in the control group(P＜0.05,P＜0.01).There was no significant difference in the central zone time and the ratio of central area time to peripheral area time in the nighttime restraint groups,and no significant difference in average speed or total distance between the daytime and nighttime restraint groups.Conclusions Male mice exhibited depression after 28 d of chronic restraint stress during the daytime,while female mice were prone to anxiety after 28 d of chronic restraint stress.Male mice experienced learning and memory impairment after 28 d of chronic restraint stress during the night.

OBJECTIVE To investigate the impact of perilla alcohol on pulmonary vascular remod-eling in hypoxia-induced pulmonary hypertension(HPH)rats and to assess its regulatory effects on the angiotensin-converting enzyme 2(ACE2)-angiotensin(1-7)[Ang(1-7)]-mas proto-oncogene receptor(Mas)and ACE-angiotensinⅡ(AngⅡ)-angiotensin type 1 receptor(AT1R)axes.METHODS An HPH rat model was established by keeping them in a hypobaric chamber that simulated an altitude of 5 000 m for 28 d.Male SD rats were randomly divided into the control group,hypoxia group,hypoxia+sildenafil group(ig administration of 30 mg·kg-1),and hypoxia+perillyl alcohol groups(ig administration of 25,50 and 100 mg·kg-1 respectively).After 28 d,the levels of glutamic-oxaloacetic transaminase(GOT),glutamic-pyruvic transaminase(GPT),and blood urea nitrogen(BUN)in rat serum were measured to evaluate the toxic effects of perillyl alcohol on rat organs.Mean pulmonary artery pressure(mPAP)was measured via right ventricular catheterization.HE staining was used to observe the patho morphological changes of pulmonary vessels in HPH rats and measure the percentages of the vascularwall area[WA(%)],wall thickness[WT(%)],lumen area[LA(%)].The right ventricular hypertrophy level and α-smooth muscle actin(α-SMA)expression level were detected by immunohistochemistry and immunofluorescence.Western blotting was used to detect the protein expression levels of α-SMA,ACE,AT1R,AngⅡ,ACE2 and Mas in lung tissues of rats.Enzyme-linked immunosorbent assay(ELISA)was employed to mea-sure the content of Ang(1-7)in lung tissues.RESULTS Compared with the control group,the serum levels of GOT,GPT and BUN in the hypoxia group rats were significantly increased,but were signifi-cantly decreased by perillyl alcohol and sildenafil intervention.Compared with the control group,mPAP,WA(%),WT(%),right ventricular inner diameter(RVID),right ventricular free wall thickness(RVFWT)and fibrosis levels were significantly increased in the hypoxia group,while LA(%)was signifi-cantly decreased.Besides,the protein expression levels of α-SMA,ACE,AT1R and AngⅡ in lung tissues were significantly elevated while those of ACE2 and Mas,as well as Ang(1-7)content were signifi-cantly decreased in hypoxia group compared to the control group.Following intervention with perillyl alcohol and sildenafil,the protein expression levels of ACE and AngⅡin lung tissues of HPH rats were significantly decreased compared to the model group while those of ACE2 and Mas receptor,along with the content of Ang(1-7),were significantly increased.Perillyl alcohol significantly reduced the protein expression level of AT1R while sildenafil had no significant effect.CONCLUSION Perillyl alcohol can lower mPAP levels by improving pulmonary vascular remodeling and reducing pulmonary vascular fibrosis in HPH rats.The mechanism may be related to the regulatory effects on the ACE-AngⅡ-AT1R and ACE2-Ang(1-7)-Mas axes.

Thoracic anesthesia with spontaneous respiration represents a form of precision anesthesia meticulously customized to individual patients.Considering the more stringent requirements this anesthesia approach imposes on the regulation of respiratory function,the writing group of the"Consensus of Experts on the Management of Thoracic Anesthesia with Spontaneous Respiration"has formulated elaborate guidelines regarding indications and contraindications,preoperative evaluation,anesthesia implementation,common complications,and treatment strategies.This was accomplished by referencing relevant domestic and international literature and integrating it with actual clinical requirements.The objective is to standardize the rational application of this anesthesia method.

Objective:To explore the changes of brain excitation/inhibition balance and gray matter volume (GMV) and their correlations with clinical features in benign childhood epilepsy with centrotemporal spikes (BECTS).Methods:A cross-sectional study was performed; 83 BECTS children enrolled from Department of Diagnostic Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2015 to January 2024 were selected as BECTS group. During the same period, 101 age- and gender-matched healthy children were recruited as healthy control group through advertisements in local primary schools. Data of conventional MRI and resting-state functional MRI (rs-fMRI) of the two groups were collected. Whole brain GMV was analyzed by voxel-based morphometry (VBM), and Hurst index was calculated based on time series data of blood oxygen level dependent (BOLD) signal of rs-fMRI. Correlations of GMV and Hurst index with disease duration and onset age in children with BECTS were explored by Pearson correlation analysis.Results:Compared with the healthy control group, the BECTS group had significantly increased GMV and decreased Hurst index in the bilateral Rolandic region ( P<0.05). Pearson correlation analysis showed that in the BECTS group, GMV in bilateral Rolandic region was negatively correlated with onset age ( r=-0.267, P=0.015) and positively correlated with disease course ( r=0.267, P=0.015); Hurst index in bilateral Rolandic region was positively correlated with onset age ( r=0.323, P=0.003) and negatively correlated with disease course ( r=-0.240, P=0.029); Hurst index was negatively correlated with GMV in bilateral Rolandic region ( r=-0.328, P=0.003). Conclusion:BECTS children have excitation/inhibition imbalance in epilepsy-related regions and cortical structural delay, and both of them are related to onset age and disease course.

Objective To investigate the effects of chronic restraint stress for 28 days(day and night)on mood and cognitive-like behavior in male and female ICR mice,to provide a basis for the selection of sex and restraint period in chronic restraint stress model animals.Methods A total of 72 male and female(1∶1)ICR mice were divided into six groups:male control,daytime restraint,and nighttime restraint groups,and female control,daytime restraint,and nighttime restraint groups.Mice in all but the control groups were bound for 10 h/d and restrained continuously for 28 days to establish a chronic restraint stress model.The emotional and cognitive behaviors induced by restraint in male and female mice at different times were observed by open field,Y maze,novel inhibition feeding,elevated cross maze,tail suspension,forced swimming,and dark-avoidance experiments.Results In the tail suspension experiment,the immobility time of male mice in the daytime restraint group was significantly increased compared with that in the control group(P＜0.05),and the immobility times of male mice in the daytime and nighttime restraint groups were also significantly increased in the forced swimming experiment,compared with those in the control group(P＜0.05).There was no significant difference between the female daytime restraint and female control groups in the novelty inhibition feeding experiment,but the feeding latency of the nighttime restraint group was significantly longer than that of the control group(P＜0.05)and the daytime restraint group(P＜0.05).The feeding latency of female mice was significantly longer than that of males during nighttime restraint(P＜0.05).In the open field test,compared with the male control group,the female control group showed a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).Compared with the female control group,the female daytime restraint group exhibited a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).There was no significant difference between the groups in the elevated cross maze and Y maze experiments.There was no significant difference in dark latency between the daytime restraint group and the control group,but darkness latency was significantly shorter in the nighttime restraint group compared with those in the control group(P＜0.05).When male and female mice were combined,the immobility time in the daytime restraint group was significantly increased in the tail suspension experiment(P＜0.05),the immobility times of mice in the daytime and nighttime restraint groups were significantly increased in the forced swimming experiment(P＜0.01,P＜0.05),and the central zone time and the ratio of central area time to peripheral area time of daytime restraint mice were significantly shorter compared with those in the control group(P＜0.05,P＜0.01).There was no significant difference in the central zone time and the ratio of central area time to peripheral area time in the nighttime restraint groups,and no significant difference in average speed or total distance between the daytime and nighttime restraint groups.Conclusions Male mice exhibited depression after 28 d of chronic restraint stress during the daytime,while female mice were prone to anxiety after 28 d of chronic restraint stress.Male mice experienced learning and memory impairment after 28 d of chronic restraint stress during the night.

To explore the application of sequential analysis in post-market safety dynamic surveillance of vaccines. Under the dynamic monitoring data of vaccines post-market approval, this research introduces the fundamental principles of maximizing sequential probability ratio test (MaxSPRT) and Bayesian sequential analysis, employing R software. Through an example of dynamic safety monitoring data of vaccines post-market approval, we analyze using the MaxSPRT and Bayesian sequential analysis. The MaxSPRT identified a safety signal in week 4 ( P<0.05), while Bayesian sequential analysis indicated that the 95% highest density interval for the RR value at week 4 is 1.13-3.27, suggesting the first appearance of a safety signal at week 4. The MaxSPRT and Bayesian sequential analysis effectively leverage continuously accumulating dynamic monitoring data, thereby serving as a valuable method for post-market safety surveillance of vaccines.

OBJECTIVE To investigate the impact of perilla alcohol on pulmonary vascular remod-eling in hypoxia-induced pulmonary hypertension(HPH)rats and to assess its regulatory effects on the angiotensin-converting enzyme 2(ACE2)-angiotensin(1-7)[Ang(1-7)]-mas proto-oncogene receptor(Mas)and ACE-angiotensinⅡ(AngⅡ)-angiotensin type 1 receptor(AT1R)axes.METHODS An HPH rat model was established by keeping them in a hypobaric chamber that simulated an altitude of 5 000 m for 28 d.Male SD rats were randomly divided into the control group,hypoxia group,hypoxia+sildenafil group(ig administration of 30 mg·kg-1),and hypoxia+perillyl alcohol groups(ig administration of 25,50 and 100 mg·kg-1 respectively).After 28 d,the levels of glutamic-oxaloacetic transaminase(GOT),glutamic-pyruvic transaminase(GPT),and blood urea nitrogen(BUN)in rat serum were measured to evaluate the toxic effects of perillyl alcohol on rat organs.Mean pulmonary artery pressure(mPAP)was measured via right ventricular catheterization.HE staining was used to observe the patho morphological changes of pulmonary vessels in HPH rats and measure the percentages of the vascularwall area[WA(%)],wall thickness[WT(%)],lumen area[LA(%)].The right ventricular hypertrophy level and α-smooth muscle actin(α-SMA)expression level were detected by immunohistochemistry and immunofluorescence.Western blotting was used to detect the protein expression levels of α-SMA,ACE,AT1R,AngⅡ,ACE2 and Mas in lung tissues of rats.Enzyme-linked immunosorbent assay(ELISA)was employed to mea-sure the content of Ang(1-7)in lung tissues.RESULTS Compared with the control group,the serum levels of GOT,GPT and BUN in the hypoxia group rats were significantly increased,but were signifi-cantly decreased by perillyl alcohol and sildenafil intervention.Compared with the control group,mPAP,WA(%),WT(%),right ventricular inner diameter(RVID),right ventricular free wall thickness(RVFWT)and fibrosis levels were significantly increased in the hypoxia group,while LA(%)was signifi-cantly decreased.Besides,the protein expression levels of α-SMA,ACE,AT1R and AngⅡ in lung tissues were significantly elevated while those of ACE2 and Mas,as well as Ang(1-7)content were signifi-cantly decreased in hypoxia group compared to the control group.Following intervention with perillyl alcohol and sildenafil,the protein expression levels of ACE and AngⅡin lung tissues of HPH rats were significantly decreased compared to the model group while those of ACE2 and Mas receptor,along with the content of Ang(1-7),were significantly increased.Perillyl alcohol significantly reduced the protein expression level of AT1R while sildenafil had no significant effect.CONCLUSION Perillyl alcohol can lower mPAP levels by improving pulmonary vascular remodeling and reducing pulmonary vascular fibrosis in HPH rats.The mechanism may be related to the regulatory effects on the ACE-AngⅡ-AT1R and ACE2-Ang(1-7)-Mas axes.