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

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

BACKGROUND: Owing to the high prevalence of antibiotic resistance in Helicobacter pylori ( H. pylori ) in China, bismuth-containing quadruple therapies have been recommended for H. pylori eradication. This study compared the efficacy and safety of quadruple regimens containing vonoprazan vs . esomeprazole for H. pylori eradication in a patient population in China. METHODS: This was a phase 3, multicenter, randomized, double-blind study. Patients with confirmed H. pylori infection were randomized 1:1 to receive quadruple therapy for 14 days: amoxicillin 1000 mg and clarithromycin 500 mg after meals, bismuth potassium citrate 600 mg before meals, plus either vonoprazan 20 mg or esomeprazole 20 mg before meals, all twice daily. The primary outcome was the eradication rate of H. pylori , evaluated using a 13 C urea breath test at 4 weeks after treatment. The non-inferiority margin was at 10%. RESULTS: The study included 510 patients, 506 of whom completed the follow-up assessment. The primary analysis revealed eradication rates of 86.8% (210/242) and 86.7% (208/240) for vonoprazan and esomeprazole therapy, respectively (treatment difference: 0.1%; 95% confidence interval [CI]: -5.95, 6.17; non-inferiority P  = 0.0009). Per-protocol analysis showed eradication rates of 87.4% for vonoprazan and 86.3% for esomeprazole (treatment difference: 1.2%; 95% CI: -5.03, 7.36; non-inferiority P  = 0.0004). Vonoprazan and esomeprazole were well tolerated, with similar safety profiles. CONCLUSION: Vonoprazan was found to be well-tolerated and non-inferior to esomeprazole for eradicating H. pylori in patients from China. TRIAL REGISTRATION ClinicalTrials.gov , NCT04198363.
Humans ; Esomeprazole/therapeutic use* ; Double-Blind Method ; Helicobacter Infections/drug therapy* ; Male ; Female ; Middle Aged ; Helicobacter pylori/pathogenicity* ; Pyrroles/therapeutic use* ; Sulfonamides/therapeutic use* ; Adult ; Clarithromycin/therapeutic use* ; Amoxicillin/therapeutic use* ; Aged ; Anti-Bacterial Agents/therapeutic use* ; Pyrrolidines/therapeutic use* ; Drug Therapy, Combination ; Proton Pump Inhibitors/therapeutic use*

Objective:To validate the application value and safety of blunt-tip needle technique for computer tomography (CT)-guided percutaneous biopsy of pancreatic lesions.Methods:Clinical data of 103 patients with pancreatic lesions undergoing CT-guided percutaneous biopsy with blunt-tip needle approach in the First Affiliated Hospital of Zhengzhou University from October 2021 to October 2023 were retrospectively analyzed, including 64 males and 39 females, aged (61.5±12.3) years. According to the access routes, procedures were divided into regular group ( n=70) and hard-to-reach group ( n=33). Technical data such as the duration of procedure, number of needle correction scans, and the incidence of complications were recorded. The technical success rate, diagnostic yield, accuracy, sensitivity, specificity, and false-negative rates were compared between groups. Results:The overall technical success rate was 100%(103/103). According to postoperative pathology and clinical follow-ups, the final diagnosis of 103 patients was 98 cases with neoplastic lesions and 5 with non-neoplastic lesions. The overall diagnostic rate of percutaneous biopsy was 91.3%(94/103), with a false negative rate of 5.8%(6/103), sensitivity of 92.9%(90/98), and specificity of 100%(90/90). Duration of procedure [(22.8±6.3) min vs. (22.4±7.9) min], number of needle correction scans [5.0 (3.0, 6.0) times vs. 5.0 (4.0, 7.5) times], length of target access [(69.9±15.4) mm vs. (73.7±17.4) mm], diagnostic yield [90.0%(63/70) vs. 93.9%(31/33)], and accuracy rate [90.0%(63/70) vs. 93.9%(31/33)] were comparable between regular group and hard-to-reach group (all P>0.05). Complications occurred in 8 patients, including 5 patients with hemorrhage and 3 with pancreatitis, which were successfully managed with conventional therapy. The incidence of complications were similar between the hard-to-reach and regular group [9.1%(3/33) vs. 7.1%(5/70), χ2=0.12, P=0.730]. Conclusion:CT-guided percutaneous biopsy in the diagnosis of pancreatic lesions with blunt-tip needle approach has a satisfactory technical success rate, diagnostic yield, accuracy, and safety, which can be used in patients with hard-to-reach lesions.

Objective To investigate the epidemiological characteristics of Mycoplasma pneumoniae(MP)infection among pediatric inpatients with respiratory tract infections(RTIs)at Children's Hospital of Hebei Province,providing evidence for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on 79 546 children hospitalized for RTIs between January 2016 and February 2024.Nasopharyngeal aspirates or deep sputum samples were collected,and polymerase chain reaction(PCR)was used to detect nucleic acids of 13 respiratory pathogens,including MP and adenovirus.The epidemiological trends across different years,seasons,genders,and age groups were analyzed.Results Among the 79 546 enrolled cases(male:47 437,59.6%;female:32 109,40.4%),the MP-positive rate was 17.7%(14 106/79 546),peaking in 2023(28.8%)and reaching the lowest in 2021(7.0%).Except for the period from July 2020 to March 2021 with exceptionally low MP positivity,epidemic peaks consistently occurred between August and February or March of the following year.Seasonal analysis revealed significantly higher MP positivity in autumn and winter compared to spring(P<0.001).Female children exhibited a higher MP-positive rate(20.1%,6444/32 109)than males(16.2%,7662/47 437)(P<0.001).The MP-positive rate increased with age:infancy(3.2%,849/26 741),toddlerhood(9.3%,1935/20 763),preschool(21.2%,3918/18 448),and school-age(54.5%,7404/13 594)(P<0.001).Co-infections with other respiratory pathogens were observed in 37.3%(5264/14 106)of MP-positive cases,with human rhinovirus(HRV)being the most frequent co-pathogen(43.3%,2279/5264 of mixed infections).Conclusion MP is a major pathogen of RTIs in hospitalized children at Children's Hospital of Hebei Province.Infections occur year-round but predominantly in autumn,with higher susceptibility in females and school-age children.Targeted preventive measures should be implemented during peak seasons to mitigate transmission risks.

Objective To investigate the learning curve of CT-guided percutaneous lung biopsy.Methods Using cumulative sum(CUSUM)analysis method,the clinical data from 110 patients,who underwent CT-guided percutaneous lung biopsy performed by the same physician at the First Affiliated Hospital of Zhengzhou University of China between May 2024 and October 2024,were retrospectively analyzed.The CUSUM learning curve was fitted,and R2 was used to assess the goodness of fit.The baseline and perioperative data were compared between different stages of the learning curve so as to determine the number of accomplished surgical cases that was required for a physician to reach the proficiency stage from the learning stage in performing CT-guided percutaneous lung biopsy.Results Successful CT-guided percutaneous lung biopsy was accomplished in all patients,with a mean operation time of(20.2+3.4)minutes(range of 15-29 minutes).With the accumulation of surgical cases,the operation time showed a gradual downward trend.The learning curve was best fitted with a cubic equation,the equation was as follows:CUSUM(110)=0.000 3x3-0.081 3x2+5.597 9x+0.774 3(where x representing the number of cases),with a goodness-of-fit coefficient R2=0.991.The fitted curve reached its peak at the performance of the 46th case,which was used as the cutoff point to divide the learning curve into two phases.Compared with the learning phase,in the proficiency phase the incidence of complications was significantly lower(pneumothorax:18.8％vs 37.0％,P=0.033)and the mean operation time was obviously shorter[(18.33+2.31)min vs(22.80±3.02)min,P＜0.001].Conclusion Through precise CUSUM analysis of the learning curves obtained from 110 patients receiving CT-guided percutaneous lung biopsy,the results of this study indicates that it requires to accomplish 46 operations before a physician can skillfully master the technique of CT-guided percutaneous lung biopsy.

Objective:To validate the application value and safety of blunt-tip needle technique for computer tomography (CT)-guided percutaneous biopsy of pancreatic lesions.Methods:Clinical data of 103 patients with pancreatic lesions undergoing CT-guided percutaneous biopsy with blunt-tip needle approach in the First Affiliated Hospital of Zhengzhou University from October 2021 to October 2023 were retrospectively analyzed, including 64 males and 39 females, aged (61.5±12.3) years. According to the access routes, procedures were divided into regular group ( n=70) and hard-to-reach group ( n=33). Technical data such as the duration of procedure, number of needle correction scans, and the incidence of complications were recorded. The technical success rate, diagnostic yield, accuracy, sensitivity, specificity, and false-negative rates were compared between groups. Results:The overall technical success rate was 100%(103/103). According to postoperative pathology and clinical follow-ups, the final diagnosis of 103 patients was 98 cases with neoplastic lesions and 5 with non-neoplastic lesions. The overall diagnostic rate of percutaneous biopsy was 91.3%(94/103), with a false negative rate of 5.8%(6/103), sensitivity of 92.9%(90/98), and specificity of 100%(90/90). Duration of procedure [(22.8±6.3) min vs. (22.4±7.9) min], number of needle correction scans [5.0 (3.0, 6.0) times vs. 5.0 (4.0, 7.5) times], length of target access [(69.9±15.4) mm vs. (73.7±17.4) mm], diagnostic yield [90.0%(63/70) vs. 93.9%(31/33)], and accuracy rate [90.0%(63/70) vs. 93.9%(31/33)] were comparable between regular group and hard-to-reach group (all P>0.05). Complications occurred in 8 patients, including 5 patients with hemorrhage and 3 with pancreatitis, which were successfully managed with conventional therapy. The incidence of complications were similar between the hard-to-reach and regular group [9.1%(3/33) vs. 7.1%(5/70), χ2=0.12, P=0.730]. Conclusion:CT-guided percutaneous biopsy in the diagnosis of pancreatic lesions with blunt-tip needle approach has a satisfactory technical success rate, diagnostic yield, accuracy, and safety, which can be used in patients with hard-to-reach lesions.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.