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.

ObjectiveTo investigate the optimal termination time for acupuncture in treating patients with acute peripheral facial paralysis and its cost-effectiveness. MethodsA total of 120 eligible patients with acute-stage peri-pheral facial paralysis were randomly assigned to either the mild dysfunction termination group and the complete recovery termination group， with 60 patients in each group. Both groups received the standard acupuncture treatment protocol. Treatment in the mild dysfunction termination group was terminated when the Sunnybrook facial grade scale （SFGS） score first reached or exceeded 83 points， while that in the complete recovery termination group was terminated when the SFGS score first reached or exceeded 95 points. Assessments were conducted before treatment， 6 and 12 months after onset. SFGS， facial disability index （FDI） including physical function （FDIp） and social function （FDIs）， self-rating anxiety scale （SAS）， and self-rating depression scale （SDS） scores were assessed before treatment， and 6 and 12 months after onset. Any acupuncture-related adverse events during treatment were recorded for safety evaluation. Treatment sessions and medical costs including direct costs， indirect costs， insurance coverage， total societal costs， and patient out-of-pocket expenses were also recorded， and an economic evaluation was conducted including cost-effectiveness ratio （CER） and incremental cost-effectiveness ratio （ICER）. ResultsUltimately， 56 patients in the mild dysfunction termination group and 55 in the complete recovery termination group completed the follow-up. At 6 and 12 months after onset， SFGS and FDIp scores in both groups improved significantly while FDIs， SAS and SDS scores decreased （P＜0.05）. Comparison of scores between groups 6 months and 12 months after onset showed no statistically significant differences （P＞0.05）. During the trial， the incidence of adverse events was 13.3% （8/60） in the mild dysfunction termination group and 18.3% （11/60） in the complete recovery termination group， with no statistically significant difference （P＞0.05）. The number of treatment sessions， total social costs， and out-of-pocket expenses in the mild dysfunction termination group were significantly lower than those in the complete recovery termination group （P＜0.05）. The CER of the mild dysfunction termination group in SFGS， FDIp， FDIs， SAS， and SDS scores was lower than that of the complete recovery termination group. The ICER analysis showed that continuing treatment until full recovery incurred an additional cost of 573.30 CNY/point in SFGS improvement， whereas 1-point improvement in FDIp， FDIs， SAS， and SDS required 21,355.25 CNY， 1779.60 CNY， 3713.96 CNY， and 2755.52 CNY， respectively. ConclusionFor acupuncture in treating acute peripheral facial palsy， terminating treatment when mild dysfunction is achieved yields long-term efficacy comparable to that of continuing treatment until complete recovery， while significantly reducing medical costs and socioeconomic burden.

Objective To investigate the relationship between the expression of serum cartilage intermediate layer protein 1(Cilp1)and myocardial fibrosis(MF)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 106 patients with T2DM(T2DM group)who were admitted to The First Hospital of Qinhuangdao were selected for this study,and 110 healthy individuals were entered into the control group.The serum Cilp1 and MF indexes[procollagen type Ⅲ-N-terminal peptide(P Ⅲ NP),galactose lectin-3(Gal-3),hyaluronic acid(HA),type Ⅲ procollagen(PCⅢ)]were detected and compared between the two groups.According to the degree of MF,there were 31,25,23,and 27 patients with stage 0,1,2,and 3 disease,respectively.The levels of serum Cilp1 and serum Cal-3,P Ⅲ NP,PC Ⅲ,HA were compared between patients of different stages.The Spearman method was applied to analyze the correlation between serum Cilp1 and MF staging,while the Pearson method was applied to analyze the correlation between serum Cilp1 and Gal-3,P Ⅲ NP,PC Ⅲ,HA.We also performed a multivariate logistic regression analysis of the influencing factors of MF 2 to 3 in patients with T2DM,and a receiver operating characteristic(ROC)curve analysis was applied to evaluate the diagnostic efficacy of serum Cilp1 level for MF 2 to 3 in patients with T2DM.Results The serum Cilp1 level in the T2DM group was higher than that in the control group(t=21.758,P＜0.05).Furthermore,the serum levels of Gal-3,P Ⅲ NP,PC Ⅲ,and HA in the T2DM group were higher than those in the control group(t=16.536-27.385,all P＜0.05),and the serum Cilp1 level in patients with T2DM positively correlated with MF staging,Gal-3,PⅢ NP,PC Ⅲ,and HA(r=0.724,0.555,0.501,0.588,0.655,all P＜0.05).The expression level of serum Cilp1 was found to be an influencing factor of MF 2 to 3 in patients with T2DM(P＜0.05).Furthermore,the ROC curve analysis showed that the area under the curve of serum Cilp1 for diagnosing MF stage 2 to 3 in patients with T2DM was 0.914.Conclusion Serum Cilp1 levels are elevated in patients with T2DM,and Cilp1 level closely relates to the formation of MF.This information can assist in clinical judgment of the degree of MF in patients with T2DM.

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 explore the correlation between the test panel of serum CC chemokine ligand 3(CCL3),soluble podoplanin(sPDPN),fatty acid-binding protein 5(FABP5)and the severity of lung injury and clinical outcomes in children with severe pneumonia.Methods A total of 168 children with severe pneumonia who visited our hospital from January 2022 to January 2023 were included in this study as severe group.The patients were assigned to good outcome group(137 cases)or poor outcome group(31 cases)based on their prognosis.Additional 80 children with mild or moderate pneumonia were treated as non-severe group.In addition,80 children who underwent health checkup were included as control group.Baseline data such as body mass index and duration of disease were observed and recorded for all children.Enzyme linked immunosorbent assay(ELISA)was applied to detect the expression levels of C-reactive protein(CRP),procalcitonin(PCT),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),CCL3,sPDPN,and FABP5 in the serum of all children.The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ)score and Lung Injury Prediction(LIPS)score were rated to evaluate the degree of lung injury.Multivariate logistic regression was used to analyze the impact of various factors on the poor outcome of children with severe pneumonia.Spearman correlation was applied to analyze the correlation between the expression levels of CCL3,sPDPN,FABP5 and poor outcome,the severity of lung injury,APACHE Ⅱ score,and LIPS score in children with severe pneumoniae.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of CCL3,sPDPN,and FABP5 expression levels for poor outcome in children with severe pneumonia.Z-test was used to compare the differences in area under the curve(AUC).Results The baseline data such as duration of disease,body mass index,age,and sex did not show significant differences among the control group,non-severe group,and severe group(P＞0.05).The levels of serum CRP,PCT,IL-6,TNF-α,CCL3,sPDPN increased,while the level of FABP5 decreased gradually from the control group to non-severe group,and severe group(P＜0.05).The patients with poor outcomes showed higher serum levels of CRP,PCT,IL-6,TNF-α,CCL3,sPDPN,APACHE Ⅱ score,and LIPS score but lower FABP5 level compared to the patients with good outcomes(P＜0.05).TNF-α,CCL3,sPDPN,APACHE Ⅱ,and LIPS scores were independent risk factors for poor outcomes in children with severe pneumonia,while FABP5 level was independent protective factor for poor outcomes in children with severe pneumonia(P＜0.05).The levels of CCL3 and sPDPN were positively correlated with APACHE Ⅱ score and LIPS score,while FABP5 was negatively correlated with APACHE Ⅱ score and LIPS score(P＜0.05).The AUC of CCL3,sPDPN,and FABP5 alone was 0.802,0.864,and 0.859 respectively for predicting poor prognosis in children with severe pneumonia.The test panel of CCL3+sPDPN+FABP5 was superior to CCL3,sPDPN,or FABP5 alone(Zcombination-CCL3=3.842,Zcombination-sPDPN=2.585,Zcombination-FABP5=2.957,P＜0.05).Conclusions The serum levels of CCL3 and sPDPN are positively correlated with the severity of lung injury,while FABP5 is negatively correlated with the severity of lung injury in children with severe pneumonia.The test panel of CCL3+sPDPN+FABP5 is valuable for predicting poor outcomes in children with severe pneumonia.

Objective To explore the correlation between the test panel of serum CC chemokine ligand 3(CCL3),soluble podoplanin(sPDPN),fatty acid-binding protein 5(FABP5)and the severity of lung injury and clinical outcomes in children with severe pneumonia.Methods A total of 168 children with severe pneumonia who visited our hospital from January 2022 to January 2023 were included in this study as severe group.The patients were assigned to good outcome group(137 cases)or poor outcome group(31 cases)based on their prognosis.Additional 80 children with mild or moderate pneumonia were treated as non-severe group.In addition,80 children who underwent health checkup were included as control group.Baseline data such as body mass index and duration of disease were observed and recorded for all children.Enzyme linked immunosorbent assay(ELISA)was applied to detect the expression levels of C-reactive protein(CRP),procalcitonin(PCT),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),CCL3,sPDPN,and FABP5 in the serum of all children.The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ)score and Lung Injury Prediction(LIPS)score were rated to evaluate the degree of lung injury.Multivariate logistic regression was used to analyze the impact of various factors on the poor outcome of children with severe pneumonia.Spearman correlation was applied to analyze the correlation between the expression levels of CCL3,sPDPN,FABP5 and poor outcome,the severity of lung injury,APACHE Ⅱ score,and LIPS score in children with severe pneumoniae.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of CCL3,sPDPN,and FABP5 expression levels for poor outcome in children with severe pneumonia.Z-test was used to compare the differences in area under the curve(AUC).Results The baseline data such as duration of disease,body mass index,age,and sex did not show significant differences among the control group,non-severe group,and severe group(P＞0.05).The levels of serum CRP,PCT,IL-6,TNF-α,CCL3,sPDPN increased,while the level of FABP5 decreased gradually from the control group to non-severe group,and severe group(P＜0.05).The patients with poor outcomes showed higher serum levels of CRP,PCT,IL-6,TNF-α,CCL3,sPDPN,APACHE Ⅱ score,and LIPS score but lower FABP5 level compared to the patients with good outcomes(P＜0.05).TNF-α,CCL3,sPDPN,APACHE Ⅱ,and LIPS scores were independent risk factors for poor outcomes in children with severe pneumonia,while FABP5 level was independent protective factor for poor outcomes in children with severe pneumonia(P＜0.05).The levels of CCL3 and sPDPN were positively correlated with APACHE Ⅱ score and LIPS score,while FABP5 was negatively correlated with APACHE Ⅱ score and LIPS score(P＜0.05).The AUC of CCL3,sPDPN,and FABP5 alone was 0.802,0.864,and 0.859 respectively for predicting poor prognosis in children with severe pneumonia.The test panel of CCL3+sPDPN+FABP5 was superior to CCL3,sPDPN,or FABP5 alone(Zcombination-CCL3=3.842,Zcombination-sPDPN=2.585,Zcombination-FABP5=2.957,P＜0.05).Conclusions The serum levels of CCL3 and sPDPN are positively correlated with the severity of lung injury,while FABP5 is negatively correlated with the severity of lung injury in children with severe pneumonia.The test panel of CCL3+sPDPN+FABP5 is valuable for predicting poor outcomes in children with severe pneumonia.

Objective To explore the mechanism of the thioredoxin-interacting protein(TXNIP)/thioredoxin-1(Trx-1)pathway in regulating the polarization of retinal microglia in rats after retinal ischemia-reperfusion(RIR)in rats,and to provide new ideas for the prevention and treatment of retinal ischemia reperfusion injury(RIRI).Methods For-ty-two healthy adult male Sprague-Dawley rats were randomly divided into a Sham group,a RIRI group and a TXNIP siRNA group.The right eye of the rats was experimented.For RIRI and TXNIP siRNA groups,RIRI models were established using the anterior chamber high intraocular pressure method.Rats in the TXNIP siRNA group were given the intravitreal injection of TXNIP siRNA 3 d before modeling.Hematoxylin-eosin(HE)staining was used to analyze retinal histopathologic changes of rats in all groups 24 h after modeling.Immunohistochemical staining of brain-specific homeobox/POU domain proteins 3A(Brn-3a)was made to count the number of retinal ganglion cells(RGCs).The dynamical changes in the number of TXNIP+cells 6 h,24 h,72 h and 7 d after modelling were analyzed through immunohistochemical staining in the RIRI group.The retinal microglia polarization and changes in the expression of TXNIP and Trx-1 proteins in each group were de-tected by double immunofluorescence staining and Western blot 24 h after modeling.Results HE staining results showed that 24 h after modelling,the retinal cells were disordered and the inner retinal layer was thickened and swelled in RIRI and TXNIP siRNA groups,compared with those in the Sham group(all P＜0.05).Immunohistochemical staining results of Brn-3a showed that 24 h after modeling,the number of Brn-3a+cells in RIRI and TXNIP siRNA groups significantly decreased,compared with that in the Sham group(both P＜0.05).The number of Brn-3a+cells in the TXNIP siRNA group was signifi-cantly higher than that in the RIRI group(P＜0.05).Immunohistochemical staining results of TXNIP at different time points after modeling showed that the expression of TXNIP+proteins started to increase 6 h after modeling.The TXNIP+protein level reached a peak at 24 h and then decreased gradually.Western blot results revealed that 24 h after modeling,RIRI and TXNIP siRNA groups had significantly higher TXNIP levels and significantly lower Trx-1 levels than the Sham group(all P＜0.05).Compared with those in the RIRI group,the expression of TXNIP proteins was significantly lower and the expression of Trx-1 proteins was significantly higher in the TXNIP siRNA group(both P＜0.05).Double immunofluores-cence staining showed that 24 h after modeling,Iba1+/CD206+cells were significantly more and Iba1+/CD16+cells were significantly less in the TXNIP siRNA group than those in the RIRI group(both P＜0.05).RIRI and TXNIP siRNA groups had significantly more Ibal+/TXNIP+cells and significantly less Iba1+/Trx-1+cells than the Sham group(both P＜0.05).The number of Iba1+/TXNIP+cells was significantly lower and the number of Iba1+/Trx-1+cells was significantly higher in the TXNIP siRNA group than those in the RIRI group(both P＜0.05).Conclusion RIR activates the TXNIP/Trx-1 path-way to induce the activation of retinal microglia and regulate the polarization of microglia,thereby resulting in RIRI in rats.

Obejective To explore whether it is possible to detect the 123I-prostate-specific membrane antigen(PSMA)radiation value of the puncture tissue during prostate biopsy to achieve real-time,rapid,and accurate identification of benign and malignant prostate tissues,so as to improve the current clinical biopsy strategy and achieve accurate diagnosis of prostate cancer during operation with fewer puncture needles.Method In this prospective,diagnostic trial,we included 29 patients with suspected prostate cancer.All patients underwent transperineal biopsy guided by ultrasound within 24 hours after injection of 123I-PSMA,a total of 435 punctures were performed.The radiation value of punctured tissue was measured in real-time with a gamma counter.Pearson test is used to correlate radiation value with histopathology.Result The median radiation value of prostate cancer tissue(1 906.50 cpm)was significantly higher than that of benign prostate tissue(415.00 cpm).The optimal cut-off value for distinguishing benign and malignant prostate tissues was 828.50 cpm.The median radiation value of clinically significant prostate cancer tissue(2 652.50 cpm)was significantly higher than that of clinically insignificant prostate cancer(1 386.00 cpm).The optimal cut-off value for distinguishing clinically significant and clinically insignificant prostate cancer tissues was 1 767.00 cpm.In additional,there was a significant positive correlation between the radiation value of puncture tissue and ISUP pathological grade(r=0.834).Conclusion It is preliminarily confirmed that detection of 123I-PSMA radiation value of prostate puncture tissue can realize real-time,rapid and accurate identification of benign and malignant prostate tissues during operation.

Objective This study aimed to investigate the effects of sleep interruption(SI)cycles on emotional behavior in ICR mice,and to establish a mouse model of comorbid anxiety and depression induced by SI.Methods Seventy-two male ICR mice(4～5 weeks old)were divided randomly into a blank group and a model group.Mice in the model group were subjected to SI stress modeling for 1,2,and 3 weeks,respectively.After modeling,emotional behaviors were evaluated using open-field,elevated plus maze,light-dark box,marble-burying,and forced-swimming tests.Serum corticosterone levels were detected by enzyme-linked immunosorbent assay.Results Mice in the model group buried significantly more marbles after 1 week of SI stress,compared with the blank group(P＜0.05).After 2 weeks of stress,mice in the model group also showed a significant decrease in the number of crossings in the light-dark box(P＜0.05)and a significant increase in the number of marbles buried(P＜0.01)compared with the control group.After 3 weeks of stress,mice in the model group showed a significant increase in the number of marbles buried(P＜0.05),a significant decrease in the number of crossings in the light-dark box(P＜0.05),and a significant increase in immobility time in the forced-swim test(P＜0.01).Conclusions ICR mice exhibited significant anxiety-related behaviors after 2 weeks of SI modeling and significant anxiety-and depressive-related behavioral changes after 3 weeks.Three weeks of SI stress can be used to establish a model of comorbid anxiety and depression.