Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Objective:To explore the effect of hyperbaric oxygen (HBO) combined with Saccharomyces boulardii in ulcerative colitis (UC) and effect of serum asymmetric dimethylarginine (ADMA). Methods:A total of 100 patients with UC admitted to the First Hospital of Yulin from August 2021 to August 2023 were prospectively selected as the study objects and divided into control group and observation group according to random number table method, with 50 cases in each group. The control group was treated with mesalazine + Saccharomyces boulardii sachets, and the observation group was treated with mesalazine + Saccharomyces boulardii sachets + HBO, and both groups were treated for 60 d. The clinical efficacy and the levels of intestinal flora, ADMA, intestinal mucosal barrier function indexes, inflammatory factors and immune function indexes before and after treatment were compared between the two groups, and the occurrence of adverse reactions were compared between the two groups. Results:After treatment, the total effective rate in the observation group was higher than that in the control group: 74.00%(37/52) vs. 50.00%(26/52), there was statistical difference ( χ2 = 5.19, P<0.05). After treatment, the number of Enterococcus and Escherichia coli in the observation group were lower than those in the control group: (4.37 ± 0.91) lgcfu/g vs. (7.95 ± 1.32) lgcfu/g, (6.17 ± 0.92) lgcfu/g vs. (9.36 ± 1.35) lgcfu/g; and the number of Lactobacillus and Bifidobacterium were higher than those in the control group: (10.24 ± 2.57) lgcfu/g vs. (8.38 ± 1.48) lgcfu/g, (10.72 ± 3.15) lgcfu/g vs. (8.69 ± 2.64) lgcfu/g, there were statistical differences ( P<0.05). After treatment, the level of ADMA in the observation group was lower than that in control group: (0.51 ± 0.08) μmol/L vs. (0.85 ± 0.12) μmol/L; and the intestinal mucosal barrier function indexes of diamine oxidase, D-lactic acid and endotoxin were lower than those in the control group: (5.82 ± 1.13) U/L vs. (7.13 ± 1.89) U/L, (3.96 ± 0.42) mmol/L vs. (4.38 ± 0.85)mmol/L, (0.18 ± 0.02) kEU/L vs. (0.23 ± 0.04) kEU/L, there were statistical differences ( P<0.05). After treatment, the inflammatory factor C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) in the observation group were lower than those in the control group: (4.84 ± 0.68) mg/L vs. (7.16 ± 0.82) mg/L, (13.24 ± 1.98) ng/L vs. (17.61 ± 2.25) ng/L, (22.13 ± 4.16) μg/L vs. (29.36 ± 5.37) μg/L; and IL-10 was higher than that in the control group:(15.35 ± 2.98) ng/L vs. (11.27 ± 3.26) ng/L, there were statistical differences ( P<0.05). After treatment, the immune function indexes CD 3+, CD 4+, CD 4+/CD 8+ in the observation group were higher than those in the control group: 0.563 ± 0.063 vs. 0.459 ± 0.052, 0.420 ± 0.049 vs. 0.383 ± 0.053, 1.35 ± 0.32 vs. 1.16 ± 0.26, there werestatistical differences ( P<0.05). The incidence of adverse reactions between the two groups had no statistical difference ( P>0.05). Conclusions:HBO combined with Saccharomyces boulardii can significantly improve clinical symptoms, reduce intestinal mucosal damage and improve intestinal microenvironment in UC patients.

Microglia are specialized immune cells in the brain, primarily responsible for clearing debris and responding to inflammation. One of the pathological features of Alzheimer's disease (AD) is the extensive activation of immune system in the brain, and the dynamic changes and dysfunction of microglia could become key factors for AD progression. This article reviews the research progress of regulated effect of microglial on AD pathology, and summarizes its potential value in AD treatment, in order to provide theoretical basis for exploring new therapeutic strategies and intervention targets for AD.

Objective To investigate the expression of microRNA-873-5p(miR-873-5p)and C-X-C motif chemokine ligand 16(CXCL16)in thyroid cancer tissue and their relationship with pathological parameters and prognosis.Methods A total of 125 patients with thyroid cancer who underwent surgery at Nanjing Sec-ond Hospital from January 2018 to June 2019 were selected as the research subjects.Some cancer tissues and corresponding adjacent tissues of the patients were collected,and the expressions of miR-873-5p and CXCL16 mRNA were detected by real-time fluorescence quantitative polymerase chain reaction.The binding sites of miR-873-5p and CXCL16 were predicted through the online database.Pearson correlation was used to analyze the correlation between miR-873-5p and CXCL16 mRNA expression,and the correlation between miR-873-5p,CXCL16 mRNA expression and pathological parameters.According to the median expression of miR-873-5p and CXCL16 mRNA in thyroid cancer tissues,they were classified as high expression and low expression.The survival curves of patients with high and low expression of miR-873-5p and CXCL16 mRNA were plotted by the Kaplan-Meier method.Taking the survival status of patients with thyroid cancer as the dependent varia-ble,Cox regression was used to determine the relationship between the expressions of miR-873-5p and CX-CL16 mRNA and the death of patients with thyroid cancer.Results The expressions of miR-873-5p and CX-CL16 mRNA in thyroid cancer tissues were 0.83±0.12 and 1.54±0.25,respectively,and those in adjacent tissues were 1.13±0.15 and 0.98±0.13,respectively,the differences were statistically significant(t=-18.160,21.089).P＜0.001).Pearson correlation analysis showed that the expression of miR-873-5p and CXCL16 mRNA in thyroid cancer tissues was negatively correlated(r=-0.722,P＜0.001).The expression of miR-873-5p in thyroid cancer tissues was negatively correlated with pathological type,TNM stage and lymph node metastasis(r=-0.510,—0.262,-0.315,P＜0.05).The expression of CXCL16 mRNA was positively correlated with pathological type,TNM stage and lymph node metastasis(r=0.593,0.275,0.314,P＜0.05).The Kaplan-Meier survival curve showed that the 5-year overall survival rate of patients with high expression of miR-873-5p was higher than that of patients with low expression of miR-873-5p.The 5-year o-verall survival rate of patients with high expression of CXCL16 mRNA was lower than that of patients with low expression of CXCL16 mRNA,and the difference was statistically significant(x2=11.328,10.514,all P=0.001).miR-873-5p≥0.84 was an independent protective factor for death in patients with thyroid cancer,and CXCL16 mRNA≥1.55 was an independent risk factor for death in patients with thyroid cancer(P＜0.05).Conclusion The expressions of miR-873-5p and CXCL16 mRNA in thyroid cancer tissues are related to patho-logical parameters and prognosis,and may become prognostic markers for patients with thyroid cancer.

Objective To establish a classification tree model for non-alcoholic fatty liver disease(NAFLD)among aircrews,screen for influencing factors of NAFLD,so as to provide scientific basis for prevention and intervention decisions for NAFLD.Methods Aircrews who underwent recuperation at a sanatorium from January 2019 to December 2023 were selected as the research objects.Their annual physical examination data were collected and the NAFLD detection rate was calculated.Age,body mass index(BMI),blood pressure,waist circumference,blood routine,biochemistry indexes,and thyroid function were incorporated,and a NAFLD risk model was constructed using classification regression tree method.The predictive performance of the NAFLD classification tree model was evaluated through model misclassification matrix,risk statistics,and receiver operating characteristic curve.Results A total of 4088 aircrews were included in the study,and NAFLD was detected in 380 persons(380/4088,9.30%).The NAFLD model consisted of three layers,and five explanatory variables affecting the onset of NAFLD were extracted,including BMI,triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT),and total bilirubin(TBIL).BMI was located at the top of the classification tree and was the most important risk factor for NAFLD in aircrews.The area under the curve(AUC)of the model was 0.853.The predictive accuracy of NAFLD was 90.9%,indicating that the model has good accuracy and fitting effect.Conclusion In this study,the detection rate of NAFLD in aircrews was 9.30%.BMI,TG,HDL-C,ALT,and TBIL are risk factors for the onset of NAFLD.NAFLD is mainly related to weight gain and lipid metabolism disorders caused by unhealthy lifestyles.

Objective:To investigate the expression of miR-1243 and long non-coding RNA (lncRNA) HULC in papillary thyroid carcinoma (PTC) tissues, and their relationships with clinicopathological features and postoperative prognosis of patients.Methods:A total of 116 PTC patients treated in the Second Hospital of Nanjing from August 2021 to August 2023 were selected. The expression levels of miR-1243 and lncRNA HULC in PTC tissues and adjacent normal tissues were detected by real-time fluorescent quantitative polymerase chain reaction (PCR). The differences in the expression levels of miR-1243 and lncRNA HULC between PTC tissues and adjacent normal tissues, as well as among PTC tissues with different clinical features and different prognoses, were analyzed. Receiver operating characteristic (ROC) curve was used to analyze the value of miR-1243 in predicting postoperative recurrence of PTC patients.Results:The relative expression level of miR-1243 in PTC tissues was significantly lower than that in adjacent normal tissues ( P<0.05), while the relative expression level of lncRNA HULC was higher than that in adjacent normal tissues ( P<0.05). The relative expression level of lncRNA HULC in PTC tissues of patients with tumor diameter ≥2 cm, tumor node metastasis (TNM) stage Ⅲ-Ⅳ, and lymph node metastasis was higher than that in patients with tumor diameter <2 cm, TNM stage Ⅰ-Ⅱ, and no lymph node metastasis (all P<0.05). The relative expression level of miR-1243 in PTC tissues of patients with TNM stage Ⅲ-Ⅳ and lymph node metastasis was lower than that in patients with TNM stage Ⅰ-Ⅱ and no lymph node metastasis (all P<0.05). There was no significant correlation between the expression of miR-1243 and lncRNA HULC in PTC tissues ( r=0.129, P=0.167). All patients were followed up for 12 months, and 20 patients had postoperative recurrence. The proportion of TNM stage Ⅲ-Ⅳ in recurrent patients was 70.00%(14/20), which was higher than that in non-recurrent patients [29.17%(28/96), P<0.05], and the relative expression level of miR-1243 was lower than that in non-recurrent patients ( P<0.05). There was no significant difference in the relative expression level of lncRNA HULC between recurrent and non-recurrent patients ( P>0.05). The area under the ROC curve of miR-1243 relative expression level in predicting postoperative recurrence of PTC patients was 0.809(95% CI: 0.711-0.907, P<0.05), with a cut-off value of 1.17, sensitivity of 65.00% and specificity of 87.50%. Conclusions:The expression of miR-1243 is down-regulated and lncRNA HULC is up-regulated in PTC tissues, and both are related to clinicopathological features such as lymph node metastasis and TNM stage. Among them, the expression of miR-1243 is related to postoperative recurrence.

Objective:To explore the effect of hyperbaric oxygen (HBO) combined with Saccharomyces boulardii in ulcerative colitis (UC) and effect of serum asymmetric dimethylarginine (ADMA). Methods:A total of 100 patients with UC admitted to the First Hospital of Yulin from August 2021 to August 2023 were prospectively selected as the study objects and divided into control group and observation group according to random number table method, with 50 cases in each group. The control group was treated with mesalazine + Saccharomyces boulardii sachets, and the observation group was treated with mesalazine + Saccharomyces boulardii sachets + HBO, and both groups were treated for 60 d. The clinical efficacy and the levels of intestinal flora, ADMA, intestinal mucosal barrier function indexes, inflammatory factors and immune function indexes before and after treatment were compared between the two groups, and the occurrence of adverse reactions were compared between the two groups. Results:After treatment, the total effective rate in the observation group was higher than that in the control group: 74.00%(37/52) vs. 50.00%(26/52), there was statistical difference ( χ2 = 5.19, P<0.05). After treatment, the number of Enterococcus and Escherichia coli in the observation group were lower than those in the control group: (4.37 ± 0.91) lgcfu/g vs. (7.95 ± 1.32) lgcfu/g, (6.17 ± 0.92) lgcfu/g vs. (9.36 ± 1.35) lgcfu/g; and the number of Lactobacillus and Bifidobacterium were higher than those in the control group: (10.24 ± 2.57) lgcfu/g vs. (8.38 ± 1.48) lgcfu/g, (10.72 ± 3.15) lgcfu/g vs. (8.69 ± 2.64) lgcfu/g, there were statistical differences ( P<0.05). After treatment, the level of ADMA in the observation group was lower than that in control group: (0.51 ± 0.08) μmol/L vs. (0.85 ± 0.12) μmol/L; and the intestinal mucosal barrier function indexes of diamine oxidase, D-lactic acid and endotoxin were lower than those in the control group: (5.82 ± 1.13) U/L vs. (7.13 ± 1.89) U/L, (3.96 ± 0.42) mmol/L vs. (4.38 ± 0.85)mmol/L, (0.18 ± 0.02) kEU/L vs. (0.23 ± 0.04) kEU/L, there were statistical differences ( P<0.05). After treatment, the inflammatory factor C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) in the observation group were lower than those in the control group: (4.84 ± 0.68) mg/L vs. (7.16 ± 0.82) mg/L, (13.24 ± 1.98) ng/L vs. (17.61 ± 2.25) ng/L, (22.13 ± 4.16) μg/L vs. (29.36 ± 5.37) μg/L; and IL-10 was higher than that in the control group:(15.35 ± 2.98) ng/L vs. (11.27 ± 3.26) ng/L, there were statistical differences ( P<0.05). After treatment, the immune function indexes CD 3+, CD 4+, CD 4+/CD 8+ in the observation group were higher than those in the control group: 0.563 ± 0.063 vs. 0.459 ± 0.052, 0.420 ± 0.049 vs. 0.383 ± 0.053, 1.35 ± 0.32 vs. 1.16 ± 0.26, there werestatistical differences ( P<0.05). The incidence of adverse reactions between the two groups had no statistical difference ( P>0.05). Conclusions:HBO combined with Saccharomyces boulardii can significantly improve clinical symptoms, reduce intestinal mucosal damage and improve intestinal microenvironment in UC patients.

Microglia are specialized immune cells in the brain, primarily responsible for clearing debris and responding to inflammation. One of the pathological features of Alzheimer's disease (AD) is the extensive activation of immune system in the brain, and the dynamic changes and dysfunction of microglia could become key factors for AD progression. This article reviews the research progress of regulated effect of microglial on AD pathology, and summarizes its potential value in AD treatment, in order to provide theoretical basis for exploring new therapeutic strategies and intervention targets for AD.

Objective:To investigate the expression of miR-1243 and long non-coding RNA (lncRNA) HULC in papillary thyroid carcinoma (PTC) tissues, and their relationships with clinicopathological features and postoperative prognosis of patients.Methods:A total of 116 PTC patients treated in the Second Hospital of Nanjing from August 2021 to August 2023 were selected. The expression levels of miR-1243 and lncRNA HULC in PTC tissues and adjacent normal tissues were detected by real-time fluorescent quantitative polymerase chain reaction (PCR). The differences in the expression levels of miR-1243 and lncRNA HULC between PTC tissues and adjacent normal tissues, as well as among PTC tissues with different clinical features and different prognoses, were analyzed. Receiver operating characteristic (ROC) curve was used to analyze the value of miR-1243 in predicting postoperative recurrence of PTC patients.Results:The relative expression level of miR-1243 in PTC tissues was significantly lower than that in adjacent normal tissues ( P<0.05), while the relative expression level of lncRNA HULC was higher than that in adjacent normal tissues ( P<0.05). The relative expression level of lncRNA HULC in PTC tissues of patients with tumor diameter ≥2 cm, tumor node metastasis (TNM) stage Ⅲ-Ⅳ, and lymph node metastasis was higher than that in patients with tumor diameter <2 cm, TNM stage Ⅰ-Ⅱ, and no lymph node metastasis (all P<0.05). The relative expression level of miR-1243 in PTC tissues of patients with TNM stage Ⅲ-Ⅳ and lymph node metastasis was lower than that in patients with TNM stage Ⅰ-Ⅱ and no lymph node metastasis (all P<0.05). There was no significant correlation between the expression of miR-1243 and lncRNA HULC in PTC tissues ( r=0.129, P=0.167). All patients were followed up for 12 months, and 20 patients had postoperative recurrence. The proportion of TNM stage Ⅲ-Ⅳ in recurrent patients was 70.00%(14/20), which was higher than that in non-recurrent patients [29.17%(28/96), P<0.05], and the relative expression level of miR-1243 was lower than that in non-recurrent patients ( P<0.05). There was no significant difference in the relative expression level of lncRNA HULC between recurrent and non-recurrent patients ( P>0.05). The area under the ROC curve of miR-1243 relative expression level in predicting postoperative recurrence of PTC patients was 0.809(95% CI: 0.711-0.907, P<0.05), with a cut-off value of 1.17, sensitivity of 65.00% and specificity of 87.50%. Conclusions:The expression of miR-1243 is down-regulated and lncRNA HULC is up-regulated in PTC tissues, and both are related to clinicopathological features such as lymph node metastasis and TNM stage. Among them, the expression of miR-1243 is related to postoperative recurrence.

Objective To summarize the best evidence of nutritional support therapy with food for special medi-cal purpose for patients undergoing adjuvant chemotherapy after oncology surgery,and to provide a reference basis for standardizing the application of food for special medical purpose and guiding clinical nutritional therapy practice for oncology patients.Methods Computer search was conducted on UpToDate,Guidelines International Network(GIN),National Guideline Clearinghouse,National Comprehensive Cancer Network,National Institute for Health and Clinical Excellence,Oncology Nursing Society,American Society for Parenteral Enteral Nutrition,European Society for Clinical Nutrition and Metabolism,Chinese Society for Parenteral and Enteral Nutrition,Joanna Briggs Institute Evidence-Based Health Care Centre database,Cochrane Library,PubMed,CINAHL,Scopus,Web of Science,Em-base,CBM,Wanfang,and China Knowledge Network on the nutritional support treatment of food for special medical purpose for postoperative adjuvant chemotherapy patients.The retrieval period was from January 2012 to August 2022.Quality evaluation of the literature was completed independently by 2 evidence-based trained researchers and combined with expert advice to extract and summarise evidence for the literature that met quality standards.Results A total of 14 articles were included,including 4 guidelines,1 clinical decision,2 systematic re views,4 expert consen-suses,and 3 randomized controlled trials.The 14 pieces of best evidence were compiled,covering 6 aspects of nu-tritional screening and assessment,nutritional education,recommended dose,formulation selection,nutritional treat-ment,and management of adverse effects.Conclusion This study summarises the best evidence on the nutritional management of food for special medical purpose in postoperative adjuvant chemotherapy patients with cancer,which is scientific and systematic.When administering nutritional therapy to patients,healthcare professionals should fully assess the nutritional status of patients,make clear and prudent choices on the dosage and type of food for special medical puipose to be used by patients,and guide patients to improve their nutritional status safely and effectively to improve their quality of life.To improve the quality of life.