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 distribution characteristics and correlation of paired oral and esophageal microbiota in patients with esophageal squamous cell carcinoma （ESCC）. MethodsA total of 46 pathologically confirmed ESCC patients were enrolled， and oral swabs and cancerous tissue samples were collected. The microbial composition was analyzed using 16S rRNA gene sequencing， and bioinformatics methods were employed to compare the microbiota diversity， compositional differences， and correlations between the two sites. ResultsThe Alpha diversity of the oral microbiota in ESCC patients was significantly higher than that of their esophageal microbiota， though the overall community structure was similar between the two sites. LEfSe analysis revealed that Spirochaetes， Prevotella， Catonella， Enterococcus， Fusobacterium periodonticum， Veillonella parvula， Capnocytophaga sputigena， and Neisseria subflava were significantly enriched in ESCC tumor tissues. In contrast， Actinobacteria， Proteobacteria， Streptococcus， Neisseria， Haemophilus， Streptococcus mitis， Haemophilus parainfluenzae， Porphyromonas gingivalis， Haemophilus haemolyticus， and Prevotella tannerae were significantly enriched in the oral cavity. Correlation analysis demonstrated significant associations between the two sites at taxonomic levels such as Spirochaetes， Treponema， Granulicatella elegans， Neisseria macacae， Treponema amylovorum， Fusobacterium periodonticum， and Neisseria meningitidis （P<0.05）. ConclusionThe oral and esophageal microbiota in ESCC patients exhibit both distinct differences and similarities. Oral microbiota may influence the esophageal microenvironment through migration or local immune modulation.

ObjectiveTo investigate the change of interleukin （IL）-18 and Th1， Th2 of CD3⁺CD8^- T helper lymphocytes in pediatric liver transplantation with cytomegalovirus （CMV） infection. MethodsA total of 40 pediatric patients who underwent pediatric liver transplantation were collected. Patients were divided into the CMV group （n=20） and the non-infected group （n=20） according to whether CMV infection occurred. The plasma IL-18 levels were determined by enzyme-linked immunosorbent assay （ELISA）. The expression percentage of IFN-γ and IL-10 of CD3⁺CD8^- T lymphocytes （Th1 and Th2） in peripheral blood were determined with flow cytometry. ResultsThe expression level of plasma IL-18 significantly increased in the CMV group compared with that in non-infected group （P<0.01）. The expression percentage of Th1 in peripheral blood significantly decreased in the CMV group compared with that in non-infected group （P<0.01）. No significant difference was found in the expression percentage of Th2 between CMV group and non-infected group. IL-18 levels were negatively correlated with the Th1 （P<0.05）. ConclusionThe elevated IL-18 levels along with polarized Th 1 subsets’ imbalance involves in the pathogenesis of CMV infection in pediatric liver transplantation.

ObjectiveTo observe the effects of Xiere Xingpi Yin （XRXPY） on the body mass and body fat distribution in patients with simple obesity， and to preliminarily explore whether the mechanism involves the regulation of specific obesity-related microRNAs （miRNAs）. MethodsA randomized controlled trial design was employed to recruit patients with simple obesity diagnosed with the traditional Chinese medicine （TCM） syndrome of dampness-heat accumulating in the spleen. Using a randomized controlled trial design， 95 patients with simple obesity of dampness-heat encumbering the Spleen syndrome were recruited， after 3 were excluded， 92 were randomly assigned in a 1∶1 ratio by means of a random number table. On the basis of lifestyle intervention， the observation group received XRXPY granules， while the control group received a placebo. Serum samples and TCM symptom scores were collected before and after the 12-week observation period. Differences in body mass loss， body composition， lipid metabolism， and TCM symptom scores were compared between the groups. An obesity-related miRNA dataset was constructed by searching the Human MicroRNA Disease Database. Library construction， sequencing， and quality control were performed on 6 selected patients from each group to screen the differentially expressed miRNAs. The intersection of these miRNAs with the obesity-related miRNAs was verified by bioinformatics and correlation analysis. ResultsBaseline characteristics were comparable between the two groups before treatment. A total of 86 patients completed the study （42 cases in the observation group and 44 cases in the control group）. The proportion of patients achieving ≥5% body weight reduction was significantly higher in the observation group than in the control group 81.0% （34/42） vs. 43.2% （19/44） （χ²=12.963， P<0.01）. Compared with baseline within the observation group， body weight， waist circumference， and TCM syndrome score were significantly decreased （P<0.01）， as were body fat percentage （P<0.01） and serum triglyceride level （P<0.05）. Compared with the control group after treatment， waist circumference and TCM syndrome score were significantly lower in the observation group （P<0.01）， and body weight showed a trend toward reduction. When changes from baseline were compared between the two groups， the magnitudes of decrease in body weight， waist circumference， and TCM syndrome score were all significantly greater in the observation group than in the control group （P<0.01）. With respect to safety， no serious adverse events occurred in either group and no participant discontinued the study because of adverse events. Compared with baseline， alanine aminotransferase levels decreased significantly in both the control and observation groups （P<0.01）， and urea decreased significantly in the observation group （P<0.01）， indicating a favorable safety profile. Sequencing identified nine differentially expressed miRNAs. After intersecting with the obesity-related miRNA dataset （187 miRNAs）， 3 miRNAs were identified： miR-221 （log₂FC=-6.62， P=0.009）， miR-29a （log₂FC=6.33， P=0.016）， and miR-10b （log₂FC=-5.91， P=0.029）. A total of 262 target genes of the 3 miRNAs were identified， which were significantly enriched in 67 pathways， including the lysine degradation pathway （P=0.001）. Correlation analysis revealed a positive correlation between miR-221 and triglycerides （r=0.46， P=0.027）， a negative correlation between miR-29a and waist-to-hip ratio （r=-0.41， P=0.047）， and positive correlations of miR-10b with body fat percentage （r=0.49， P=0.014） and waist circumference （r=0.44， P=0.032）. ConclusionXRXPY combined with lifestyle intervention can effectively reduce the body mass and improve body composition. The underlying mechanism may involve the regulation of the lysine degradation pathway via miR-221， miR-29a， and miR-10b， though further verification is required.

ObjectiveTo observe the effects of Xiere Xingpi Yin （XRXPY） on the body mass and body fat distribution in patients with simple obesity， and to preliminarily explore whether the mechanism involves the regulation of specific obesity-related microRNAs （miRNAs）. MethodsA randomized controlled trial design was employed to recruit patients with simple obesity diagnosed with the traditional Chinese medicine （TCM） syndrome of dampness-heat accumulating in the spleen. Using a randomized controlled trial design， 95 patients with simple obesity of dampness-heat encumbering the Spleen syndrome were recruited， after 3 were excluded， 92 were randomly assigned in a 1∶1 ratio by means of a random number table. On the basis of lifestyle intervention， the observation group received XRXPY granules， while the control group received a placebo. Serum samples and TCM symptom scores were collected before and after the 12-week observation period. Differences in body mass loss， body composition， lipid metabolism， and TCM symptom scores were compared between the groups. An obesity-related miRNA dataset was constructed by searching the Human MicroRNA Disease Database. Library construction， sequencing， and quality control were performed on 6 selected patients from each group to screen the differentially expressed miRNAs. The intersection of these miRNAs with the obesity-related miRNAs was verified by bioinformatics and correlation analysis. ResultsBaseline characteristics were comparable between the two groups before treatment. A total of 86 patients completed the study （42 cases in the observation group and 44 cases in the control group）. The proportion of patients achieving ≥5% body weight reduction was significantly higher in the observation group than in the control group 81.0% （34/42） vs. 43.2% （19/44） （χ²=12.963， P<0.01）. Compared with baseline within the observation group， body weight， waist circumference， and TCM syndrome score were significantly decreased （P<0.01）， as were body fat percentage （P<0.01） and serum triglyceride level （P<0.05）. Compared with the control group after treatment， waist circumference and TCM syndrome score were significantly lower in the observation group （P<0.01）， and body weight showed a trend toward reduction. When changes from baseline were compared between the two groups， the magnitudes of decrease in body weight， waist circumference， and TCM syndrome score were all significantly greater in the observation group than in the control group （P<0.01）. With respect to safety， no serious adverse events occurred in either group and no participant discontinued the study because of adverse events. Compared with baseline， alanine aminotransferase levels decreased significantly in both the control and observation groups （P<0.01）， and urea decreased significantly in the observation group （P<0.01）， indicating a favorable safety profile. Sequencing identified nine differentially expressed miRNAs. After intersecting with the obesity-related miRNA dataset （187 miRNAs）， 3 miRNAs were identified： miR-221 （log₂FC=-6.62， P=0.009）， miR-29a （log₂FC=6.33， P=0.016）， and miR-10b （log₂FC=-5.91， P=0.029）. A total of 262 target genes of the 3 miRNAs were identified， which were significantly enriched in 67 pathways， including the lysine degradation pathway （P=0.001）. Correlation analysis revealed a positive correlation between miR-221 and triglycerides （r=0.46， P=0.027）， a negative correlation between miR-29a and waist-to-hip ratio （r=-0.41， P=0.047）， and positive correlations of miR-10b with body fat percentage （r=0.49， P=0.014） and waist circumference （r=0.44， P=0.032）. ConclusionXRXPY combined with lifestyle intervention can effectively reduce the body mass and improve body composition. The underlying mechanism may involve the regulation of the lysine degradation pathway via miR-221， miR-29a， and miR-10b， though further verification is required.

Objective To investigate the preventive and therapeutic effects of ethanol extracts derived from three sources of traditional Chinese medicine: Stellera chamaejasme L., Euphorbia fischeriana Steud. and Euphorbia kansuensis Prokh., on imiquimod （IMQ）-induced psoriasis in mice. Methods Thirty-six male BALB/c mice were randomly divided into the following 6 groups with 6 mice in each group: blank control, model, Stellera chamaejasme, Euphorbia fischeriana, Euphorbia kansuensis, and calcipotriol. Psoriasis area and severity index（PASI） scores were used to record the changes of skin lesions in every group; Hematoxylin-eosin（HE） staining was used to observe the pathological morphology of skin and measure the thickness of the epidermis. Immunohistochemistry was used to detect the expression of nuclear antigen Ki67 in the skin tissues of mice. Results Compared with the model group, the three kinds of ethanol extracts could reduce the PASI score, inhibit epidermal thickening, and decrease expression of Ki67 in the psoriasis mice. Among them, the therapeutic effect of Stellera chamaejasme was the most significant and it was better than the commonly used topical drug calcipotriol. Conclusion The ethanol extract of Stellera chamaejasme had good anti-psoriatic activity, which could inhibit the abnormal proliferation of keratinocytes, reduce the expression of Ki67, and significantly improve psoriasis-like skin lesions.

Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.

Objective To provide a comprehensive review of the modeling method of the empty bottle stimulation(EBS)anxiety model,including commonly used experimental animal strains and genders,animal grouping,modeling procedures,modeling duration,primary behavioral evaluation method,and the underlying pathological mechanisms.This aims to offer a reference for the application of the EBS anxiety model in anxiety disorder research.Methods Searches were conducted in databases such as CNKI and PubMed to collect all literature related to the EBS anxiety model,which were then systematically summarized and organized.Results(1)Male adult SD or Wistar rats are predominantly used as experimental animals;(2)The optimal modeling period is 2 weeks;(3)Behavioral evaluations primarily utilize the open field test,elevated plus maze test,and light-dark box test;(4)Pathological mechanisms involve abnormal neurotransmitter metabolism in brain regions such as the hippocampus,prefrontal cortex,and amygdala.Conclusions The EBS anxiety model exhibits an anxiety-like behavioral phenotype and associated neurobiological mechanisms,validating its utility as an animal model for the study of anxiety disorders.However,further exploration and refinement are required for its standardized construction protocol and the understanding of its mechanistic underpinnings.

Objective:To investigate the effect of ERMAP on imiquimod(IMQ)-induced psoriasis-like skin inflammation in mice and its related mechanism.Methods:The experimental mice were divided into 3 groups:Sham group,WT group and ERMAP-/-group,with 9 mice in each group.The Sham group was smeared with Vaseline,and the WT group and ERMAP-/-group were smeared with IMQ to induce psoriatic dermatitis.The severity of IMQ-induced psoriasis lesions in mice were evaluated according to the psoria-sis area and severity index(PASI)and the HE staining pathology score.The expressions of F4/80 and Ki67 in mouse skin lesions were observed by immunofluorescence staining.The relative expressions of IL-1β,IL-6,IFN-γ and iNOS in skin lesions were detected by qRT-PCR.Flow cytometry was used to detect the proliferation and activation of T cells and the proportion of macrophages in spleen.Results:In the IMQ-induced mouse model of psoriasis-like dermatitis,the skin lesions of ERMAP gene knock out mice showed more severe squamous accumulation and skin bulge,more inflammatory cells aggregation and cytokine production,and the proportion of immune cells in the spleen of mice increased compared with the WT group,and the proportion of M1 macrophages increased.Conclu-sion:ERMAP deficiency aggravates IMQ-induced psoriasis-like skin inflammation in mice by enhancing immune response.