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 evaluate the correlation between serum CTRP12 and carotid atherosclerosis(CAS)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 200 T2DM patients from Bengbu Medical University Third Affilated Hospital were enrolled in this study and divided into T2DM group(n=94),CAS group(n=106).Healthy subjects were selected as normal control(NC,n=50)group.Serum CTRP12 level was determined by ELISA.CTRP12 and baseline indicators were compared among the groups.Relationship between CTRP12 and each biochemical index were evaluated by Pearson or Spearman analysis as appropriate.Multiple linear regression analysis was used to explore the influencing factors for CTRP12.Logistic regression analysis was used to explore the influencing factors for CAS.Results DBP,HbA1c,TC,LDL-C and IL-6 in the three groups were increased successively(P<0.05),while CTRP12 were decreased successively(P<0.05).BMI,FPG,TG and HOMA-IR in T2DM and CAS groups were higher than those in NC group(P<0.05),HDL-C was lower than that in NC group(P<0.05),SBP in CAS group was higher than that in NC and T2DM groups(P<0.05).Pearson or Spearman correlation analysis showed that serum CTRP12 was negatively correlated with BMI,SBP,DBP,FPG,HbA1c,TC,TG,LDL-C,IL-6 and HOMA-IR(P<0.05),and positively correlated with HDL-C(P<0.05).Multiple linear regression analysis showed that FPG,LDL-C and IL-6 were the influential factors for CTRP12.Logistic regression analysis showed that TC,HbA1c and CTRP12 were risk factors for the occurrence of CAS in patients with T2DM.Conclusions CTRP12 is closely related to CAS,and reduced serum CTRP12 level is an independent risk factor for T2DM with CAS.

Pregnancy with chronic kidney disease (CKD), particularly in stages 4-5, carries high risks of adverse outcomes including maternal renal failure, preeclampsia/eclampsia, fetal growth restriction, and preterm birth. This report described a 26-year-old woman with congenital solitary kidney, polycystic ovaries, and uterine septum due to PAX2 gene variant, complicated by CKD stage 4. Through multidisciplinary team precision management and individualized treatment strategies, including timely initiation of dialysis, the patient successfully maintained pregnancy until 34 +1 weeks and delivered a female infant via cesarean section. This case summarizes key management experiences for end-stage renal disease in pregnancy, highlighting early risk assessment, precise nutritional management, hemodialysis protocol optimization, and the crucial role of multidisciplinary collaboration, providing valuable references for managing CKD-complicated pregnancies.

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OBJECTIVE: To observe the characteristics of changes in non-invasive hemodynamic parameters in neonates with septic shock so as to provide clinical reference for diagnosis and treatment. METHODS: A observational study was conducted. The neonates with sepsis complicated with septic shock or not admitted to neonatal intensive care unit (NICU) of the First Affiliated Hospital of Shantou University Medical College were enrolled as the study subjects, who were divided into preterm infant (< 37 weeks) and full-term infant (≥ 37 weeks) according to the gestational age. Healthy full-term infants and hemodynamically stable preterm infants transferring to NICU after birth were enrolled as controls. Electronic cardiometry (EC) was used to measure hemodynamic parameters, including heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), stroke volume index (SVI), cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR) and systemic vascular resistance index (SVRI), before treatment in the septic shock group, at the time of diagnosis of sepsis in the sepsis without shock group, and before the discharge from the obstetric department or on the day of transferring to NICU in the control group. RESULTS: Finally, 113 neonates with complete data and parental consent for non-invasive hemodynamic monitoring were enrolled, including 32 cases in the septic shock group, 25 cases in the sepsis without shock group and 56 cases in the control group. In the septic shock group, there were 17 cases at the compensated stage and 15 cases at the decompensated stage. There were 21 full-term infants (20 cured or improved and 1 died) and 11 premature infants (7 cured or improved and 4 died), with the mortality of 15.62% (5/32). There were 18 full-term infants and 7 premature infants in the sepsis without shock group and all cured or improved without death. The control group included 28 full-term infants and 28 premature infants transferring to NICU after birth. Non-invasive hemodynamic parameter analysis showed that SV, SVI, CO and CI of full-term infants in the septic shock group were significantly lower than those in the sepsis without shock group and control group [SV (mL): 3.52±0.99 vs. 5.79±1.32, 5.22±1.02, SVI (mL/m²): 16.80 (15.05, 19.65) vs. 27.00 (22.00, 32.00), 27.00 (23.00, 29.75), CO (L/min): 0.52±0.17 vs. 0.80±0.14, 0.72±0.12, CI (mL×s^-1×m^-2): 40.00 (36.67, 49.18) vs. 62.51 (56.34, 70.85), 60.01 (53.34, 69.68), all P < 0.05], while SVR and SVRI were significantly higher than those in the sepsis without shock group and control group [SVR (kPa×s×L^-1): 773.46±291.96 vs. 524.17±84.76, 549.38±72.36, SVRI (kPa×s×L^-1×m^-2): 149.27±51.76 vs. 108.12±12.66, 107.81±11.87, all P < 0.05]. MAP, SV, SVI, CO and CI of preterm infants in the septic shock group were significantly lower than those in the control group [MAP (mmHg, 1 mmHg ≈ 0.133 kPa): 38.55±10.48 vs. 47.46±2.85, SV (mL): 2.45 (1.36, 3.58) vs. 3.96 (3.56, 4.49), SVI (mL/m²): 17.60 (14.20, 25.00) vs. 25.50 (24.00, 29.00), CO (L/min): 0.32 (0.24, 0.63) vs. 0.56 (0.49, 0.63), CI (mL×s^-1×m^-2): 40.01 (33.34, 53.34) vs. 61.68 (56.68, 63.35), all P < 0.05], while SVR and SVRI were similar to the control group [SVR (kPa×s×L^-1): 1 082.88±689.39 vs. 656.63±118.83, SVRI (kPa×s×L^-1×m^-2): 126.00±61.50 vs. 102.37±11.68, both P > 0.05]. Further analysis showed that SV, SVI and CI of neonates at the compensation stage in the septic shock group were significantly lower than those in the control group [SV (mL): 3.60±1.29 vs. 4.73±1.15, SVI (mL/m²): 19.20±8.33 vs. 26.34±3.91, CI (mL×s^-1×m^-2): 46.51±20.34 vs. 61.01±7.67, all P < 0.05], while MAP, SVR and SVRI were significantly higher than those in the control group [MAP (mmHg): 52.06±8.61 vs. 48.54±3.21, SVR (kPa×s×L^-1): 874.95±318.70 vs. 603.01±111.49, SVRI (kPa×s×L^-1×m^-2): 165.07±54.90 vs. 105.09±11.99, all P < 0.05]; MAP, SV, SVI, CO and CI of neonates at the decompensated stage in the septic shock group were significantly lower than those in the control group [MAP (mmHg): 35.13±6.08 vs. 48.54±3.21, SV (mL): 2.89±1.17 vs. 4.73±1.15, SVI (mL/m²): 18.50±4.99 vs. 26.34±3.91, CO (L/min): 0.41±0.19 vs. 0.65±0.15, CI (mL×s^-1×m^-2): 43.34±14.17 vs. 61.01±7.67, all P < 0.05], while SVR and SVRI were similar to the control group [SVR (kPa×s×L^-1): 885.49±628.04 vs. 603.01±111.49, SVRI (kPa×s×L^-1×m^-2): 114.29±43.54 vs. 105.09±11.99, both P > 0.05]. CONCLUSIONS Full-term infant with septic shock exhibit a low cardiac output, high vascular resistance hemodynamic pattern, while preterm infant with septic shock show low cardiac output and normal vascular resistance. At the compensated stage the hemodynamic change is low output and high resistance type, while at the decompensated stage it is low output and normal resistance type. Non-invasive hemodynamic monitoring can assist in the identification of neonatal septic shock and provide basis for clinical diagnosis and treatment.
Humans ; Shock, Septic/physiopathology* ; Infant, Newborn ; Hemodynamics ; Female ; Male ; Case-Control Studies ; Infant, Premature

BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans ; Heart Defects, Congenital/mortality* ; Male ; Female ; China/epidemiology* ; Infant ; Child, Preschool ; Adult ; Child ; Adolescent ; Infant, Newborn ; Middle Aged ; Young Adult ; Aged ; Rural Population

Objective:To evaluate the interventional effect of online mental health education for subthreshold depression (SD) in elderly individuals.Methods:Using a randomized controlled trial (RCT) design, a total of 105 older adults with SD were recruited from 6 long-term care (LTC) settings in Ningbo city between September and November in 2023. The subjects were randomized to a intervention group (35 cases), a control group (35 cases) and a waiting list group (35 cases) in a 1∶1∶1 ratio using a random number generator. The intervention method was mental health education, comprising basic knowledge of depressive symptoms, knowledge and skills of cognitive therapy, knowledge and skills of behavioral therapy and life education for the elderly. The intervention group received online mental health education, while the control group was given face-to-face mental health education. After the intervention group and control group have completed the intervention and post-intervention data collection, the waiting list group would choose either online or face-to-face mental health education independently based on personal preference. The 3 groups received identical interventions with a 4-week duration. During the intervention and follow-up periods, 7 cases dropped out, resulting in 34 cases in the intervention group, 31 in the control group, and 33 in the waiting list group being included in the final analysis. The 3 groups were checked-up with the Center for Epidemiologic Studies Depression Scale (CES-D), Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item (GAD-7) at baseline, post-intervention and 6-month follow-up. One-way ANOVA and χ2 tests were employed to compare the baseline characteristics across the 3 groups. Mixed-effects model for repeated measures were employed to compare mean between-group differences and mean changes for each group at each time point, with the specific aim of analyzing the intervention effect of online mental health education for SD in older adults. Results:There was no statistically significant differences in the baseline characteristics among the 3 groups (all P>0.05). The time × group interaction effects of CES-D, PHQ-9, and GAD-7 scores were significant across 3 groups ( Finteraction=6.58, 7.24, 8.42) (all P<0.01). Further pairwise comparisons revealed that the CES-D, PHQ-9, and GAD-7 scores in the intervention group were all significantly lower than those in the waiting list group [(14.36±4.56) vs (15.51±3.21), (5.13±2.46) vs (7.20±2.62), (4.63±2.41) vs (7.13±2.42)], and all significantly lower than those in the control group [(14.36±4.56) vs (15.53±3.19), (5.13±2.46) vs (6.32±2.57), (4.63±2.41) vs (6.23±2.41)] at post-intervention (all P<0.05). The PHQ-9 and GAD-7 scores in the intervention group were both significantly lower than those in the control group [(4.62±2.35) vs (6.23±2.20), (4.72±2.38) vs (6.26±2.32)] at 6-month follow-up (both P<0.001). Conclusion:Online mental health education may alleviate depressive and anxiety symptoms among older adults with SD, and it may be equally effective as face-to-face mental health education.

Objective To explore the feasibility and safety of ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer.Methods Totally 84 patients who underwent ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer were enrolled,and the technical success rate,complete ablation rate,complication rate,pain relief rate and survival time,etc.were observed.Results The median age of 84 cases was 61.5 years.Totally 86 tumors,including 44.19％(38/86)at the head/neck and 55.81％(48/86)at the body/tail of pancreas were detected,and a total of 85 ablation sessions were performed with the median ablation energy applied per tumor of 9.90(1.08,21.60)kJ and the complete ablation rate of 42.86％(36/84).The technical success rate was 100％(85/85).Thirty-nine complication events occurred in 25 cases,no ablation-related death.Among 34 patients underwent ablation mainly for pain symptoms,the pain score decreased from(6.22±1.12)points before treatment to(1.94±1.64)points after treatment(P＜0.001).During 6.8(3.3,12.9)months' follow-up,the mean survival time was(8.5±6.7)months,and all 47 patients died due to tumor progression.Conclusion Ultrasound-guided percutaneous microwave ablation was safe and feasible for unresectable pancreatic cancer.

Objective:To construct a diagnostic prediction model for childhood asthma and conduct a preliminary evaluation based on the test results of specific IgE (sIgE) for airborne allergens and in combination with clinical data.Methods:This study is a case-control study. A total of 4 338 cases that completed the sIgE test for airborne allergens in the Allergy Department of Beijing Children′s Hospital Affiliated to Capital Medical University from January to December 2023 were selected as the research subjects. They were divided into the asthma group and the non-asthma group based on the diagnostic information. Age, gender, cough and wheezing symptoms, and the classification results of sIgE concentrations of 15 airborne allergens were collected as the predictor variables of the asthma diagnostic prediction model. Differential analysis and LASSO regression were employed for the screening of predictor variables. The multivariate logistic regression method was applied to construct the nomogram prediction model. The data set was randomly split at a ratio of 7∶3 into a training set (3 036 cases) for constructing the prediction model and a validation set (1 302 cases) for testing the predictive efficacy of the model. The area under the receiver operating characteristic (ROC) curve (AUC), the Hosmer-Lemeshow calibration curve were utilized to assess the discrimination and goodness of fit of the model, and the clinical decision curve (DCA) was adopted to evaluate the clinical application value of the model.Results:Among 4 338 pediatric cases, children aged 0 to <3 years accounted for 10.17% (441 cases), those aged 3 to <6 years accounted for 36.49% (1 583 cases), those aged 6 to <12 years accounted for 46.98% (2 038 cases), and those aged 12 to 18 years accounted for 6.36% (276 cases). Males constituted 65.17% (2 827 cases), and females 34.83% (1 511 cases). The proportion of children without wheezing symptoms was 41.47% (1 799 cases), while those with wheezing symptoms was 58.53% (2 539 cases). The asthma group accounted for 41.77% (1 812 cases), and the non-asthma group for 58.23% (2 526 cases). Statistically significant differences were observed between the asthma group and the non-asthma group in 18 predictive variables including age, gender, wheezing symptoms, d1, d2, e1, e5, g2, g6, m6, t11, t3, t6, w1, w22, w6, wx5, and m3 ( P<0.05). LASSO regression analysis identified six predictor variables: age (calculated in months), cough and wheezing symptoms, and sIgE of four airborne allergens, namely, Dermatophagoides pteronyssinus (d1), Canis familiaris dander (e5), Aspergillus fumigatus (m3), and Artemisia vulgaris pollen (w6).Multifactorial regression analysis revealed that the contribution degrees of the above-mentioned predictor variables to the asthma diagnosis prediction model were ranked as follows: cough and wheezing symptoms ( OR=24.37, P<0.001), m3 ( OR=1.34, P<0.001), d1 ( OR=1.22, P<0.001), e5 ( OR=1.12, P=0.028), w6 ( OR=1.11, P<0.001), and age ( OR=1.01, P<0.001).The AUCs of the nomogram prediction model for the training set and the validation set were 0.853 (95% CI: 0.840-0.866) and 0.838 (95% CI: 0.817-0.860), respectively. The Hosmer-Lemeshow calibration curve indicated a good fit ( P=0.215 for the training set; P=0.352 for the validation set). The DCA of the validation set demonstrated that when the probability threshold for predicting the occurrence of childhood asthma was 8%-92%, the model had the best applicability. Conclusion:By combining age, cough and wheezing symptoms, and sIgE of the four airborne allergens (d1, e5, m3, and w6) selected from 15 airborne allergens, a childhood asthma diagnosis prediction model with good predictive performance and clinical practicability was constructed. It can serve as a simple and convenient tool for accurately identifying asthma and provides a practical basis for the application of artificial intelligence big data analysis models in the prevention, treatment, and management of childhood asthma.

Objective Focusing on gynecological surgery,we constructed a prediction model for surgical duration by extracting features from unstructured surgical planning texts and integrating multimodal data via artificial intelligence technology.Methods The clinical data of 34 614 patients who underwent gynecologic surgeries at West China Second University Hospital,Sichuan University between January 2022 and October 2024 were collected.An embedding-transformer model was constructed to convert surgical planning texts into a one-dimensional numerical feature,referred to as the step feature.The predictive value of the step feature was assessed by comparing the performance improvements of linear regression,random forest,eXtreme Gradient Boosting(XGBoost),support vector regression,K-nearest neighbor regression,and artificial neural network algorithms in two scenarios—with and without the step feature as an input.The out-of-sample prediction accuracy of the models was assessed using mean absolute error(MAE),root mean squared error(RMSE),and R-squared(R2).Furthermore,the model interpretability was examined using SHapley Additive exPlanations(SHAP)values.Results SHAP results showed that the step feature had the highest predictive contribution.Temporal factors in surgical scheduling also influenced gynecological surgery duration.The XGBoost model demonstrated optimal performance on the test set,significantly improving prediction accuracy with a 40.43%increase in R2,while reducing MAE and RMSE by 21.27%and 20.13%,respectively,compared to the baseline model without the step feature.Conclusion The embedding-transformer model developed in this study effectively extracts features from surgical planning texts and enhances the predictive performance of machine learning models.The XGBoost prediction model can assist hospital administrators in implementing more refined management of gynecological surgeries and improving the utilization efficiency of surgical resources.