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.

BACKGROUND:The formation of postoperative abdominal adhesions is a complicated process,and the prevention of postoperative adhesions is an urgent problem in clinic. OBJECTIVE:To analyze the mechanism of adhesion at cellular and molecular levels,and to provide theoretical basis for the prevention and treatment of adhesion by mesenchymal stem cell exosomes. METHODS:"Abdominal adhesion,pelvic adhesion,postoperative adhesion,epithelial mesenchymal transformation,mesenchymal stem cells,stem cell exosomes,mesenchymal stem cell exosomes"were selected as Chinese and English search terms.We searched PubMed,CNKI,and Chinese biomedical literature and screened relevant articles on postoperative abdominal adhesion and mesenchymal stem cell exosomal intervention published from inception to August 2023.After systematic analysis,54 articles were finally included for the review. RESULTS AND CONCLUSION:(1)Any pathological factors such as peritoneal inflammation,mechanical injury,tissue ischemia,and foreign body implantation cause peritoneal surface injury,resulting in postoperative abdominal adhesion.The formation process of adhesion includes the interaction of peritoneal mesothelial cell repair,inflammatory response,fibrinolytic system,coagulation pathway and other processes,involving a variety of cytokines and signaling pathways.Wnt/β-catenin pathway can induce fibrosis and angiogenesis,and cooperate with transforming growth factor-β/Smads signaling pathway to stimulate fibroblast proliferation and cause peritoneal fibrosis.Meanwhile,nuclear factor-κB signaling pathway up-regulates the expression of cellular inflammatory factors,promotes fibroblast proliferation,and plays a key role in the process of tissue fibrosis.(2)The paracrine function of stem cells is an important direction of molecular intervention in abdominal adhesions based on regenerative medicine.It can participate in a variety of complex cytokines and signaling pathways involved in abdominal adhesions.(3)Compared with traditional methods for treating abdominal adhesions,mesenchymal stem cell exosome has biological activity and is safe to use.Mesenchymal stem cell exosomes without special culture and expansion have lower immunogenicity,longer stability and other advantages,can guide a normal repair and healing through a variety of ways.(4)Mesenchymal stem cell exosome has been proven to be involved in regulating the above processes of adhesion formation in previous studies,showing potential application prospects in clinical studies.However,further clinical studies are needed to explore appropriate treatment options for mesenchymal stem cell exosomes to address the problem of clinical translation.

Objective To investigate dynamic changes in myocardial protein phosphorylation during the acute phase of myocardial infarction (MI) in mice. Methods Six 8-week-old C57BL/6J mice were randomly assigned to MI model (n＝3) or sham-operated control (n＝3) groups. Cardiac tissues were harvested 72 hours post-intervention for proteomic analysis. Phosphorylation modifications were systematically characterized using liquid chromatography-mass spectrometry (LC-MS). Bioinformatics analyses included differential phosphorylation screening, functional enrichment, hierarchical clustering, and protein-protein interaction network. Results LC-MS identified 1 921 differentially phosphorylated sites (20 tyrosine and 1 901 serine/threonine sites) across 851 proteins. Compared with controls, MI hearts exhibited significant phosphorylation upregulation at 1 545 sites and downregulation at 376 sites (P＜0.05). Conclusions This study delineates MI-associated phosphorylation dynamics, providing mechanistic insights and potential therapeutic targets for acute MI intervention.

Objective: To investigate the prevalence and associated factors of spinal curvature abnormalities among primary and secondary school students in the Guangxi Zhuang Autonomous Region, so as to provide a scientific basis for the prevention and control of such abnormalities. Methods: From September to November 2023, adopting a stratified cluster random sampling method, spinal curvature screenings and questionnaire surveys were conducted among 168 931 students from grade 4 of primary school to grade 12 of high school in 111 districts and counties across 14 cities in Guangxi. Chi square tests and binary Logistic regression analysis were used to analyze influencing factors of spinal curvature abnormalities. Results: In 2023, the detection rate of poor posture among students above grade 4 in Guangxi was 4.24% , and the detection rate of spinal curvature abnormalities was 2.13%. The detection rate was higher among urban students (2.84%) than rural students (1.66%), boarding students (2.61%) than non-boarding students (1.60%), and high school students (3.16%) than junior high (2.45%) and primary school students (1.15%), and the differences were statistically significant ( χ 2=269.85, 221.44, 565.10, P <0.01). A trend of increasing detection rates with higher grade levels was observed ( χ 2 trend =617.63, P <0.01). Binary Logistic regression analysis indicated that students without boarding at school ( OR =0.82, 95% CI =0.75-0.90), engaging in high-intensity physical activity for over 60 min per day ≥5 days per week ( OR =0.90, 95% CI =0.82-0.98), and adequate sleep ( OR =0.87, 95% CI =0.81-0.94) had lower risks of detecting spinal curvature abnormalities ( P <0.05). Conclusions The prevalence of spinal curvature abnormalities increases with grade level among primary and secondary school students in Guangxi. Regular moderate-to-vigorous physical activity demonstrates protective effects against spinal abnormalities.

Objective To establish a mouse model of bronchiectasis with acute infection and evaluate the immunogenicity and protective effect of a self-assembling Pseudomonas aeruginosa(PA)nanoparticle vaccine rePO-FN based on fusion of PcrV-OprI(rePO)protein with self-assembling ferritin(Ferritin).Methods ① SPF-grade female C57BL/6 mice(aged 6～8 weeks,weighing 18～20 g)were randomly allocated into normal saline group,and low-,medium-and high-dose elastase groups(n=6).A mouse model of bronchiectasis was established via intratracheal instillation of different doses of elastase(30 μL of normal saline containing 0.65,1.30 and 2.60 IU elastase)for 3 consecutive days.At 14 and 21 d after modeling,ELISA and HE staining were performed respectively to detect the concentration of IL-6 and to observe pathological changes in lung tissue in order to confirm the modeling.② A recombinant plasmid encoding the gene of fusion protein rePO-FN was constructed and expressed in E.coli.The target protein was purified via affinity chromatography and renatured to obtain the desired protein.The physicochemical properties of the rePO-FN protein were characterized using SDS-PAGE protein gel electrophoresis,dynamic light scattering,molecular sieve chromatography,and transmission electron microscopy.③ C57BL/6J mice were randomly divided into PBS group,rePO group,rePO-FN group,and Ferritin group(n=10).The mice in the above groups were immunized intramuscularly with 100 μL PBS buffer alone or containing 10 μg of corresponding proteins on days 0,7,and 14.ELISA was used to measure the specific antibodies in serum.In 7 d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the PBS,rePO,and rePO-FN groups.After establishing a bronchiectasis model by intratracheal instillation of 2.60 IU of elastase in C57BL/6J mice as described above,the mice were randomly divided into bronchiectasis PBS group,bronchiectasis rePO group,and bronchiectasis rePO-FN group(n=10).Immunization was conducted at the same dose and procedure as described above,in 21 d after bronchiectasis modeling.At the 7th d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the groups.Results ①Repeated intratracheal instillation of elastase significantly increased the concentration of IL-6 in the lung tissue when compared to the content of the normal saline group(P＜0.05).Pathological observations revealed varying degrees of bronchial wall destruction,alveolar fusion,edema,neutrophil infiltration,and hemorrhage,with the severity increasing with elastase dose,which confirming successful establishment of the mouse model of bronchiectasis.② Well-dispersed rePO-FN nanoparticles were successfully prepared,with an average particle size of 91.28 nm,a Zeta potential of approximately-6.5 mV,and a polydispersity index(PDI)of 0.306.Molecular sieve chromatography determined the elution volume of rePO-FN protein to be 8.80 mL,corresponding to a molecular weight of approximately 1 400 kDa.③ Under acute PA XN-1 strain infection,the survival rate of the rePO-FN immunization group and the bronchiectasis rePO-FN immunization group were significantly higher than that of the PBS control group(P＜0.05).Additionally,bacterial colonization in the lung tissues was significantly lower in the rePO-FN immune group and the bronchiectasis rePO-FN immune group under acute PA XN-1 strain infection than that in the rePO group and the bronchiectasis rePO group(P＜0.05).Conclusion Our vaccine rePO-FN can effectively trigger a strong humoral immune response and provide significant protection against PA infection in a mouse bronchiectasis model.

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Objective:To investigate the differences of the glymphatic system (GS) function between patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and healthy controls and between different seizure types by using diffusion tensor imaging along perivascular space (DTI-ALPS), and to analyze the correlation between GS function and the course of disease, as well as the efficacy of predicting the surgical outcome.Methods:This study was a cross-sectional study. A total of 171 patients with mTLE-HS (mTLE-HS group) and 75 healthy volunteers (HC group) were retrospectively enrolled from July 2009 to July 2021 at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University. The general information of all subjects, such as seizure type (partial seizure, secondary generalized seizure), surgical outcome, etc., was analyzed. The 3D magnetization prepared rapid gradient echo T 1WI and DTI sequence images were collected. The VBM analysis method was used to segment cerebrospinal fluid and calculate the volume. The ALPS index of the bilateral brain was calculated using the Atlas-based DTI-ALPS method. Independent sample t-test or paired t test were used to compare the ALPS index between the mTLE-HS group and HC group, and between patients with different seizure types. Pearson correlation analysis was used to analyze the correlation between bilateral ALPS index and disease duration in mTLE-HS group. The predictive value of the ALPS index for surgical outcomes was evaluated by receiver operating characteristics curve and area under the curve. Results:Among the 171 mTLE-HS patients, 98 patients were mTLE with left-side HS (mTLE-LHS) and 73 patients were mTLE with right-side HS (mTLE-RHS); 37 patients underwent surgical treatment, including 27 with good prognosis and 10 with poor prognosis. Compared with the HC group, the left-side ALPS index of mTLE-LHS and mTLE-RHS were both decreased ( P<0.05). The right-side ALPS index in mTLE-RHS was lower than that in the HC group ( P<0.001). There was no significant difference in the right-side ALPS index between mTLE-LHS and HC group ( P=0.080). The ALPS index on the affected side of patients with secondary generalized seizures was significantly lower than that of patients with only partial seizures (all P<0.05), but the difference in ALPS index on the healthy side was not statistically significant( P>0.05). The left-side and right-side ALPS index in mTLE-LHS were negatively correlated with disease duration ( r=-0.272, P=0.007; r=-0.307, P=0.002), but no significant correlation was found between the left-side or right-side ALPS index in mTLE-RHS (all P>0.05). The DTI-ALPS index on the affected side in mTLE-HS patients exhibited good diagnostic accuracy for surgical outcome classification, with an area under the curve of 0.778. Conclusions:The patients with mTLE-HS exhibit dysfunction of the GS, and the degree of impairment is related to the type of seizure and the course of epilepsy. The ALPS index, which characterizes the function of GS, demonstrates good diagnostic accuracy for classifying surgical outcomes.

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.