Fabry disease(FD) is a rare X-linked inherited lysosomal storage disorder caused by reduced or absent α-galactosidase A(α-Gal A) activity.This deficiency leads to the pathological accumulation of metabolic substrates,resulting in multiorgan dysfunction affecting the heart,kidneys and brain,and potentially threatening life.In addition to symptomatic treatment,the current specific therapeutic approaches for FD in clinical practice primarily include enzyme replacement therapy(ERT),such as agalsidase alfa,agalsidase beta,and pegunigalsidase alfa-iwxj,as well as molecular chaperone therapy(e.g.,migalastat).These therapies not only help stabilize patient symptoms but also significantly reduce the disease burden.Substrate reduction therapy(SRT) and gene therapy are currently in various stages of clinical trials.SRT can be administered as a monotherapy or in combination with ERT,while gene therapy offers the potential to correct α-Gal A deficiency through a single administration.Additionally,several emerging therapeutic strategies,including drug delivery systems based on nanotechnology,are under active investigation.This paper summarizes the mechanisms,approved drugs,and their advantages and disadvantages of these treatment approaches,and discusses the progress of clinical trials for each therapy.Additionally,it explores potential future directions for the development of treatment strategies for FD.

AIM:To investigate the correlation be-tween vitamin D levels and urinary incontinence in women with type 2 diabetes mellitus(T2DM).METHODS:A total 366 female T2DM patients who were hospitalized in Department of Endocrinology,First Hospital of Lanzhou University from May 2022 to July 2023 were selected and were classified as vi-tamin D deficiency(＜20 ng/mL),insufficiency(20-30 ng/mL),and sufficiency(＞30 ng/mL)according to serum 25-hydroxyvitamin D[25(OH)D]concen-tration.The prevalence of urinary incontinence and severity was compared among three groups.Ad-justed logistic regression was used to analyze the correlation between vitamin D levels and urinary in-continence and its subtypes.RESULTS:Of the 366 patients,174(47.5％)T2DM with urinary inconti-nence.25(OH)D level was significantly lower in group with urinary incontinence than without(11.9 ng/mL vs.17.8 ng/mL,P＜0.01).The prevalence of urinary incontinence and moderate and severe uri-nary incontinence was significantly higher in group with vitamin D deficiency than groups with insuffi-ciency and sufficiency(P＜0.05).Adjusted logistic re-gression analysis showed that vitamin D deficiency was associated with an increased risk of any incon-tinence and urgency incontinence compared to vi-tamin D sufficiency(P＜0.05),vitamin D insufficien-cy was not associated with urinary incontinence.Age,BMI,parity and low 25(OH)D levels were inde-pendent risk factors for combined urinary inconti-nence in women with T2DM.CONCLUSION:Vita-min D deficiency is significantly associated with the risk of urinary incontinence in women with T2DM,and appropriate vitamin D supplementation may have some benefits for urinary incontinence.

ObjectiveTo observe the effect of enriched environment (EE) combined with acupuncture at head point (HA) on behavior in rats with autism spectrum disorder. MethodsHealthy female Wistar rats were given peritoneal injection of sodium valproate at 12.5 days of gestation. Twenty-four male offspring rats were randomly selected and then randomly divided into model group (n = 6), EE group (n = 6), HA group (n = 6) and EE combined with HA group (the combined group, n = 6). Six male offspring rats born from female mice injected with the same amount of saline intraperitoneally were as control group. After four weeks of treatment, all the five groups were tested with three-chamber test and marble burying test, and the sociability index, the social novelty index and the number of buried marbles were recorded. The levels of interleukin (IL)-1β and IL-6 in peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). ResultsAfter treatment, compared with the model group, the sociability index and the social novelty index improved (P < 0.05), the number of buried marbles reduced (P < 0.05), and the levels of IL-6 and IL-1β in peripheral blood decreased in EE group, HA group and the combined group (P < 0.05); while the combined group was the best (P < 0.01). ConclusionBoth EE or acupuncture at HA could improve behavioral symptoms, and reduce the expression of inflammatory factors in rats with autism spectrum disorder. The combination of the two methods showed the best result.

Objective To investigate whether quercetin inhibits pyroptosis of mouse fibroblast NIH-3T3 cells by regulating the NLRP3/caspase-1/GSDMD signaling pathway.Methods NIH-3T3 cells were treated with quercetin or MCC950(a specific inhibitor of NLRP3)before stimulation with lipopolysaccharide(LPS)and ATP to induce cell pyroptosis.The optimal quercetin concentration and duration were screened using the CCK-8assay after testing various concentrations and times.Morphological changes of the treated cells was observed,and the levels of IL-18 and IL-1β in the cell culture supernatant were detected with ELISA;the protein expressions of NLRP3,cleaved caspase-1,and GSDMD-N and the mRNA levels of NLRP3,caspase-1 and GSDMD were detected using Western blotting and qRT-PCR.The changes in cell pyroptosis were examined with TUNEL staining and LDH release assay.Results The CCK-8 assay indicated that 24-hour treatment with 20 μmol/L quercetin yielded the most favorable results.LPS and ATP stimulation of NIH-3T3 cells induced obvious swelling,cell membrane rupture and leakage of cell contents,significantly increased IL-18 and IL-1β levels,and enhanced protein expressions of NLRP3,cleaved caspase-1 and GSDMD-N and mRNA levels of NLRP3,caspase-1 and GSDMD.LPS and ATP stimulation also caused a significant increment of TUNEL-positive cell counts and LDH release in NIH-3T3 cells.Treatment with quercetin or MCC950 significantly reduced cell pyroptosis induced by LPS and ATP,lowered the concentrations of IL-18 and IL-1β,decreased the expression levels of NLRP3,caspase-1/cleaved caspase-1,GSDMD/GSDMD-N,and reduced the number of TUNEL-positive cells and LDH release.Conclusion Quercetin suppresses pyroptosis of mouse fibroblasts stimulated with LPS and ATP and reduces secretion of inflammatory cytokines by inhibiting the NLRP3/caspase-1/GSDMD pathway.

Objective To investigate whether quercetin inhibits pyroptosis of mouse fibroblast NIH-3T3 cells by regulating the NLRP3/caspase-1/GSDMD signaling pathway.Methods NIH-3T3 cells were treated with quercetin or MCC950(a specific inhibitor of NLRP3)before stimulation with lipopolysaccharide(LPS)and ATP to induce cell pyroptosis.The optimal quercetin concentration and duration were screened using the CCK-8assay after testing various concentrations and times.Morphological changes of the treated cells was observed,and the levels of IL-18 and IL-1β in the cell culture supernatant were detected with ELISA;the protein expressions of NLRP3,cleaved caspase-1,and GSDMD-N and the mRNA levels of NLRP3,caspase-1 and GSDMD were detected using Western blotting and qRT-PCR.The changes in cell pyroptosis were examined with TUNEL staining and LDH release assay.Results The CCK-8 assay indicated that 24-hour treatment with 20 μmol/L quercetin yielded the most favorable results.LPS and ATP stimulation of NIH-3T3 cells induced obvious swelling,cell membrane rupture and leakage of cell contents,significantly increased IL-18 and IL-1β levels,and enhanced protein expressions of NLRP3,cleaved caspase-1 and GSDMD-N and mRNA levels of NLRP3,caspase-1 and GSDMD.LPS and ATP stimulation also caused a significant increment of TUNEL-positive cell counts and LDH release in NIH-3T3 cells.Treatment with quercetin or MCC950 significantly reduced cell pyroptosis induced by LPS and ATP,lowered the concentrations of IL-18 and IL-1β,decreased the expression levels of NLRP3,caspase-1/cleaved caspase-1,GSDMD/GSDMD-N,and reduced the number of TUNEL-positive cells and LDH release.Conclusion Quercetin suppresses pyroptosis of mouse fibroblasts stimulated with LPS and ATP and reduces secretion of inflammatory cytokines by inhibiting the NLRP3/caspase-1/GSDMD pathway.

Objective:To investigate the prevalence and potential classification of symptoms after total knee arthroplasty (TKA) in patients with knee osteoarthritis (KOA), and to analyze the differences in demographic characteristics and surgical data, compare the different potential subgroups, in order to provide a basis for clinical symptom management plans.Methods:This study was a multicenter cross-sectional survey. Through convenience sampling, patients with KOA undergoing TKA in the orthopaedic wards of four tertiary hospitals in Urumqi were selected as the study from November 2023 to February 2024. The study subjects were surveyed using a general information questionnaire, the Visual Analogue Scale (VAS) for pain, the Hospital Anxiety and Depression Scale (HADS), and the Pitts Burgh Sleep Quality Index (PSQI), and the degree of postoperative joint swelling and size of ecchymosis were measured. Latent class analysis was performed using Mplus 8.3 software, and Logistic regression analysis was conducted using SPSS 26.0 software to explore the influencing factors of the latent classes.Results:Totally 337 effective questionnaires were collected, and the recovery rate was 94.7% (337/356), and the age distribution ranged from 47 to 85 (65.19 ± 6.99) years old, with 90 (26.7%) males and 247 (73.3%) females. There were 92.3% (311/337) of TKA patients with postoperative symptom cluster. The symptom cluster of patients with TKA were identified as 3 classes. They were named as "high level pain-psychological disorder group"(12.5%, 39/311), "high bruises-moderate psychological disorders group"(25.4%, 79/311) and "low symptom burden group" (62.1%, 193/311). The results of the unordered multi-class logistic regression analysis showed that age 45-59 years ( OR = 2.367), body mass index 24.0-27.9 kg/m 2 ( OR = 0.207), living with children/parents ( OR = 6.473), and this being the second joint surgery ( OR = 0.040) were the factors influencing the "high level pain-psychological disorders group" (all P<0.05). The factors influencing the "high bruises-moderate psychological disorders group" were living with children/parents ( OR = 4.023), comorbid chronic diseases ( OR = 1.979, 3.842), and intraoperative blood loss ≤100 ml ( OR = 2.342) (all P<0.05). Conclusions:The postoperative symptom cluster of TKA patients have a relatively high incidence, and there is heterogeneity within the symptom cluster, so nurses need to identify at-risk patients early according to the characteristics of different categories and give interventions.

AIM:To explore the correlation between trimethylamine-N-oxide(TMAO)and type 2 diabetic kidney disease(DKD),and to provide new ideas for the early clinical diagnosis of DKD.METHODS:A total 246 patients with type 2 diabetes mellitus(T2DM)ad-mitted to the Department of Endocrinology of the First Hospital of Lanzhou University from January 1,2020 to May 31,2020 were divided into diabetic kidney disease group(DKD group)and simple diabetes mellitus group(NDKD group).According to urinary albumin/creatinine ratio(UACR),the patients were divided into A1,A2 and A3 subgroups.According to the estimated glomerular filtration rate(eGFR),the patients were divided into G1,G2,G3 and G4-5 sub-groups.According to the Kidney Disease:Improving Global Outcomes(KDIGO)guidelines,the risk of progression of DKD was assessed(low,medium,high or very high risk).General clinical data and laboratory indicators were collected.TMAO level was measured by euzymelinked immunosorbent assay.SPSS 25.0 software was used for statistical analysis.RESULTS:In T2DM patients,TMAO level was positively correlated with UACR(r=0.515,P<0.01)and negatively correlated with eGFR(r=-0.409,P<0.01).TMAO is an indepen-dent risk factor for the onset and progression of DKD.In diagnostic model,the AUROC was 0.745 with op-timal cut-off value was 5.37μmol/L.CONCLUSION:TMAO is closely related to the occurrence and de-velopment of DKD,and it has certain clinical predictive value for DKD.Therefore,TMAO may become a po-tential target for the early diagnosis and treatment of DKD.

AIM:To investigate the correlation be-tween vitamin D levels and urinary incontinence in women with type 2 diabetes mellitus(T2DM).METHODS:A total 366 female T2DM patients who were hospitalized in Department of Endocrinology,First Hospital of Lanzhou University from May 2022 to July 2023 were selected and were classified as vi-tamin D deficiency(＜20 ng/mL),insufficiency(20-30 ng/mL),and sufficiency(＞30 ng/mL)according to serum 25-hydroxyvitamin D[25(OH)D]concen-tration.The prevalence of urinary incontinence and severity was compared among three groups.Ad-justed logistic regression was used to analyze the correlation between vitamin D levels and urinary in-continence and its subtypes.RESULTS:Of the 366 patients,174(47.5％)T2DM with urinary inconti-nence.25(OH)D level was significantly lower in group with urinary incontinence than without(11.9 ng/mL vs.17.8 ng/mL,P＜0.01).The prevalence of urinary incontinence and moderate and severe uri-nary incontinence was significantly higher in group with vitamin D deficiency than groups with insuffi-ciency and sufficiency(P＜0.05).Adjusted logistic re-gression analysis showed that vitamin D deficiency was associated with an increased risk of any incon-tinence and urgency incontinence compared to vi-tamin D sufficiency(P＜0.05),vitamin D insufficien-cy was not associated with urinary incontinence.Age,BMI,parity and low 25(OH)D levels were inde-pendent risk factors for combined urinary inconti-nence in women with T2DM.CONCLUSION:Vita-min D deficiency is significantly associated with the risk of urinary incontinence in women with T2DM,and appropriate vitamin D supplementation may have some benefits for urinary incontinence.

OBJECTIVE: To propose a sensitivity test method for geometric correction position deviation of cone-beam CT systems. METHODS: We proposed the definition of center deviation and its derivation. We analyzed the influence of the variation of the three-dimensional spatial center of the steel ball point, the projection center and the size of the steel ball point on the deviation of geometric parameters and the reconstructed image results by calculating the geometric correction parameters based on the Noo analytical method using the FDK reconstruction algorithm for image reconstruction. RESULTS: The radius of the steel ball point was within 3 mm. The deviation of the center of the calibration parameter was within the order of magnitude and negligible. A 10% Gaussian perturbation of a single pixel in the 3D spatial coordinates of the steel ball point produced a deviation of about 3 pixel sizes, while the same Gaussian perturbation of the 2D projection coordinates of the steel ball point produced a deviation of about 2 pixel sizes. CONCLUSION The geometric correction is more sensitive to the deviation generated by the three-dimensional spatial coordinates of the steel ball point with limited sensitivity to the deviation generated by the two-dimensional projection coordinates of the steel ball point. The deviation sensitivity of a small diameter steel ball point can be ignored.
Algorithms ; Calibration ; Cone-Beam Computed Tomography ; Steel

BACKGROUND: Textbook outcome (TO) can guide decision-making among patients and clinicians during preoperative patient selection and postoperative quality improvement. We explored the factors associated with achieving a TO for gallbladder carcinoma (GBC) after curative-intent resection and analyzed the effect of adjuvant chemotherapy (ACT) on TO and non-TO patients. METHODS: A total of 540 patients who underwent curative-intent resection for GBC at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2020 were retrospectively analyzed. Multivariable logistic regression was used to investigate the factors associated with TO. RESULTS: Among 540 patients with GBC who underwent curative-intent resection, 223 patients (41.3%) achieved a TO. The incidence of TO ranged from 19.0% to 51.0% across the study period, with a slightly increasing trend over the study period. The multivariate analysis showed that non-TO was an independent risk factor for prognosis among GBC patients after resection ( P = 0.003). Age ≤60 years ( P = 0.016), total bilirubin (TBIL) level ≤34.1 μmol/L ( P <0.001), well-differentiated tumor ( P = 0.008), no liver involvement ( P <0.001), and T1-2 stage disease ( P = 0.006) were independently associated with achieving a TO for GBC after resection. Before and after propensity score matching (PSM), the overall survival outcomes of non-TO GBC patients who received ACT and those who did not were statistically significant; ACT improved the prognosis of patients in the non-TO group ( P <0.05). CONCLUSION Achieving a TO is associated with a better long-term prognosis among GBC patients after curative-intent resection, and ACT can improve the prognosis of those with non-TO.
Humans ; Middle Aged ; Gallbladder Neoplasms/pathology* ; Retrospective Studies ; Prognosis ; Hepatectomy ; Cholecystectomy