Objective To investigate the clinical features and etiology of bilateral middle cerebellar peduncle lesion. Methods A retrospective analysis was performed for the clinical and imaging data of 59 patients who underwent cranial magnetic resonance imaging （MRI） in Central Hospital Affiliated to Dalian University of Technology and Yellow River Sanmenxia Hospital and were found to have abnormal signals of bilateral middle cerebellar peduncles， and a descriptive analysis was performed. Results As for clinical manifestations， among the 59 patients， there were 23 patients with unilateral limb weakness， 21 patients with dizziness， 12 patients with slurred speech， 8 patients with walking instability and limb numbness， 2 patients with drinking cough， dysphagia， double vision， and weakness of both lower limbs， 1 patient with limb tremor and bradykinesia， and 3 patients without symptoms. As for clinical diagnosis， among the 59 patients， there were 42 with Wallerian degeneration， 4 with acute cerebral infarction， 3 with demyelinating diseases of the central nervous system， 3 with hypertensive encephalopathy， 2 with multiple system atrophy， 1 with parkinsonism， 1 with the possibility of neuronal intranuclear inclusion disease， 1 with hypoparathyroidism and intracranial calcification， 1 with central nervous system lymphoma， and 1 with the possibility of ischemic or metabolic encephalopathy. Conclusion There are complex and diverse etiologies for bilateral middle cerebellar peduncle lesion， with Wallerian degeneration as the most common clinical diagnosis. Other diseases， such as acute cerebrovascular disease， inflammatory demyelinating diseases， neurodegenerative diseases， neoplastic diseases， and inherited metabolic diseases， can also be comorbid with bilateral middle cerebellar peduncle lesion.

Bawei Chenxiang Powder(BCP), first documented in the Tibetan medical work Four Medical Classics, has been widely applied in clinical practices in Tibetan and Mongolian medicines since its development. It has the effect of clearing the heart heat, calming the mind, and inducing resuscitation. On the basis of BCP, multiple types of formulae have been developed, such as Bawei Yiheyi Chenxiang Powder, Bawei Rang Chenxiang Powder, and Bawei Pingchuan Chenxiang Powder, which are widely used for treating cardiovascular and respiratory diseases. Current pharmacological research has revealed the pharmacological effects of BCP and its related formulae against myocardial ischemia, cerebral ischemia, renal ischemia, and anti-hypoxia. BCP and its related formulae introduced more treatment options for related clinical diseases and provided insights for fully comprehending the essence and pharmacological components of the formulae. This paper systematically reviewed the clinical and pharmacological research on BCP and its related formulae, analyzing the formulation principles and potential key flavors and active ingredients. This lays a fundamental scientific basis for the clinical use, quality evaluation, and subsequent development and application of BCP and its related formulae, providing references for studying traditional Chinese medicine formulae in a thorough and systematic manner.
Drugs, Chinese Herbal/chemistry* ; Humans ; Powders/chemistry* ; Animals ; Medicine, Chinese Traditional

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

OBJECTIVE: Photodynamic therapy has become an important method in clinical tumor treatment. This study aimed to investigate the effects of hematoporphyrin on multiple myeloma (MM) and its potential applications. METHODS: The MM cell line RPMI 8226 was treated with hematoporphyrin derivative (HPD), and CCK-8 assay was used to determine cell viability, apoptosis was detected by flow cytometry, intracellular reactive oxygen species (ROS) levels were measured using a detection kit combined with flow cytometry, and Western blot assay was used to detect apoptosis-related proteins and key signaling pathway protein levels. RESULTS: The optimal incubation time for the maximum absorption of HPD in RPMI 8226 cells was 4 hours. HPD significantly inhibited the proliferation of RPMI 8226 cells in a dose- and illumination time-dependent manner ( r =0.981; r =0.961). Additionally, HPD induced apoptosis in RPMI 8226 cells, but had no significant inhibitory effect on peripheral blood mononuclear cells derived from healthy individuals. HPD combined with illumination treatment significantly increased the intracellular ROS level, upregulated the expression of apoptosis-related proteins such as cleaved PARP, cleaved caspase-3 and Bax, and down-regulated the expression of proteins that maintain cell survival, such as NF-κB and Akt. CONCLUSION The HPD can inhibit the proliferation and induce apoptosis of multiple myeloma cells.
Humans ; Multiple Myeloma/pathology* ; Hematoporphyrins/pharmacology* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Cell Proliferation/drug effects* ; Photochemotherapy ; Cell Survival/drug effects* ; Signal Transduction

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective:This study evaluates the horizontal sound localization ability of young and middle-aged individuals with symmetric sensorineural hearing loss (SNHL) in noisy environments. It also examines the impact of hearing loss severity and signal-to-noise ratio (SNR) on localization accuracy.Methods:In this cross-sectional study, conducted from April 2023 to April 2024, 135 young and middle-aged patients (73 males and 62 females, aged 18-60 years) with SNHL who sought care at Beijing Chaoyang Hospital, were categorized into mild, moderate, and moderate-to-severe hearing loss groups (45 per group), with 45 normal-hearing controls (23 males and 22 females, aged 20-60 years). Participants completed localization tasks in quiet and noisy environments with SNR levels of 5 dB, 0 dB, -5 dB, and-10 dB. Root mean square error (RMSE) was used to measure localization accuracy. Repeated measures ANOVA assessed the effects of hearing loss and SNR on RMSE, while, Pearson correlation evaluated the relationship between binaural 4-frequency pure-tone average (4fPTA) and RMSE. Multiple linear regression analyzed the predictive role of 4fPTA and age.Results:(1) Two-way repeated measures ANOVA showed that both hearing loss severity and SNR significantly affected RMSE ( F=92.67, P<0.01; F=430.29, P<0.01), with a significant interaction between the two factors( F=92.67, P<0.01). (2) RMSE increased with hearing loss severity. At SNRs of 5 dB, 0 dB, and-5 dB, the moderate-to-severe group had significantly higher RMSE than the mild and moderate groups ( P<0.01). No significant differences were found between mild and moderate groups ( P=0.53, 0.57, 0.22). At-10 dB SNR, significant differences were observed across all groups ( P<0.01). (3) RMSE increased non-linearly as SNR decreased. Mean RMSE values under quiet conditions and at SNRs of 5 dB, 0 dB, -5 dB, and-10 dB were (7.43±5.01)°, (9.80±5.74)°, (11.60±6.22)°, (14.56±7.07)°, and (18.74±8.02)°, respectively. (4) RMSE was significantly positively correlated with binaural 4fPTA ( r=0.54-0.58, P<0.01). Multiple linear regression analysis indicated that the binaural average 4fPTA significantly predicted RMSE ( P<0.01), explaining 30.5%-34.1% of RMSE variance. Age did not significantly contribute to RMSE variation. Conclusions:The degree of hearing loss and background noise SNR significantly affect horizontal sound localization in young and middle-aged SNHL patients. RMSE increases with hearing loss severity and decreases with higher SNR. The interaction between hearing loss and SNR is significant, and RMSE correlates with binaural 4fPTA. However, the regression model based on 4fPTA and age explains only part of the RMSE variance, suggesting other contributing factors.

Objective:To explore the relationship between parenting styles of toddlers aged 30 months and attention deficit hyperactivity disorder (ADHD) symptom trajectories in preschool children.Methods:The subjects were 2 111 children and their parents in Ma'anshan Birth Cohort. Parenting styles were assessed at 30 months of age using the Brief Toddler Parenting Style Questionnaire, which defines parenting styles on four dimensions: warmth and interaction, attention and acceptance, outdoor and social activities, and neglect and restrictions. The Chinese version of the Conners Abbreviated Symptom Questionnaire was used to examine preschooler's ADHD symptoms aged 3, 5, and 6 years. ADHD symptom trajectories were fitted using group-based trajectory modeling. The multinomial logistic regression model was used to evaluate the relationship between parenting styles at 30 months of age and ADHD symptom trajectories in children. The additive and multiplicative models were applied to analyze the interaction effect of negative parenting styles in children's ADHD symptom trajectories.Results:ADHD symptom trajectories in children included the low-score (48.3%), moderate-score (47.7%), and high-score groups (4.0%). After adjusting for the confounding factors, the results of the multinomial logistic regression analysis showed that negative parenting styles of the father/mother were associated with ADHD symptom trajectories in children ( P<0.05). The father/mother's low warmth and interaction (father: OR=2.07,95% CI:1.68-2.54; mother: OR=2.02,95% CI:1.64-2.48), low attention and acceptance (father: OR=1.94,95% CI:1.57-2.39; mother: OR=1.47,95% CI:1.20-1.81), low outdoor and social (father: OR=1.74,95% CI:1.43-2.13; mother: OR=1.60,95% CI:1.32-1.94), and high neglect and restriction (father: OR=2.09,95% CI:1.67-2.62; mother: OR=2.06,95% CI:1.65-2.56) were associated with ADHD symptom moderate-score trajectories compared to the low-score trajectory group, mother's low warmth and interaction, low outdoor and social, and high neglect and restrictions. Statistically significant association was seen in negative parenting styles of fathers with the high-score group. There was a multiplicative interaction for hostile parenting ( P<0.05). The additive interaction results showed that there was a synergistic effect of hostile parenting, which increased the risk of the high-score trajectories of ADHD symptoms in children. Conclusions:Both parents' parenting styles influenced ADHD symptom change the trajectories in preschoolers. Negative parenting styles of the father/mother increase the risk of the moderate-score and high-score trajectories of ADHD symptoms in children. Hostile parenting by both parents has a synergistic impact on the risk of ADHD symptom trajectories in children, and the simultaneous presence of both increases the risk of the high-score trajectory of ADHD symptoms.

Objective:To evaluate the efficacy and safety of rivaroxaban and investigate the clinical features of Mycoplasma pneumoniae pneumonia (MPP) associated with pulmonary thromboembolism (PTE) in children. Methods:A case series study was conducted on 36 children, diagnosed with MPP associated with PTE and hospitalized in our institution from January 2020 to June 2024 of Department of Pediatric Respiratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University. Clinical data and follow-up information were collected to analyze their clinical characteristics, outcomes, and adverse events to rivaroxaban. Comparison of coagulation indices before and after treatment with rivaroxaban using the Mann-Whitney rank sum test.Results:Among the 36 children, there were 27 males and 9 females, and the age of onset was (7.8±2.8) years. PTE was diagnosed (17±6) days after the onset of MPP. Thirty-four cases (94%) were classified as low-risk PTE, and 13 cases (36%) had thromboembolism of multiple anatomic sites. All patients presented with cough and fever, manifesting as shortness of breath in 33 cases (92%), chest pain in 12 case (33%), hemoptysis in 6 case (17%) and dyspnea in 5 cases (14%). Pulmonary artery involvement was demonstrated by CT pulmonary angiography in all 36 children. The D-dimer level was 5.1 (4.2, 12.2) mg/L. D-dimer levels were 5.1 (4.2, 12.2) mg/L, of which 29 cases (81%) were ≥4.0 mg/L. The total duration of anticoagulation 3.1 (2.5, 4.2) months. All children received rivaroxaban for 2.7 (2.2, 3.8) months. Of the 36 children, 35 cases were followed up after 3 months of anticoagulant therapy, and 30 cases (83%) showed pulmonary artery thrombus absorption. Finally, follow-up outcome data were available for 34 cases, of which 33 showed complete resolution of thrombus in the affected areas, and 1 showed partial resolution. There were no cases of death, thrombus recurrence or progression, major bleeding events occurred or chronic thromboembolic pulmonary hypertension. Adverse events included hemoptysis in 2 cases and elevated liver enzymes in 4 cases. After the treatment of rivaroxaban, the levels of D-dimer were decreased compared with those before the treatment of PTE (0.3 (0.2, 0.5) vs. 5.1 (4.2, 12.2) mg/L, Z=-7.12, P<0.05), and the levels of prothrombin time levels were significantly longer compared with those before the treatment of PTE (3.6 (12.4, 14.9) vs. 13.0 (11.8, 13.6) s, Z=2.34, P<0.05). Conclusions:During the course of MPP, the emergence of clinical symptoms such as short of breath, chest pain, hemoptysis, dyspnea or along with elevated D-dimer levels, should raise suspicion for the occurrence of PTE. Rivaroxaban has shown good efficacy and a favorable safety profile.