The first case of multiple myeloma treated with ASCT followed by Anti-BCMA CAR-T cells using retrovirus vector: A case report.

Chimeric antigen receptor T (CAR-T)-cell therapy targeting B-cell maturation antigen (BCMA) is currently one of the promising treatment methods for relapsed/refractory multiple myeloma (MM). Herein, this study is a case report on a 41-year-old male patient with MM. Unfortunately, he still developed multidrug-resistant, refractory, and bone marrow suppression after receiving multiline high-intensity chemotherapy. After a detailed evaluation, the physician recommended autologous hematopoietic stem cell transplantation (ASCT) support, followed by sequential immunotherapy with autologous anti- BCMA CAR-T cells. The CAR-T product is a novel anti-BCMA CAR-T based on Retrovirus vectors (RV). It was worth noting that the patient achieved VGPR (very good partial remission) one month after infusion of anti-BCMA CAR-T cells. Recent tests have found that the M protein was no longer detectable and the patient has achieved CR (complete response). Although grade 3 cytokine release syndrome (CRS) appeared, the symptom was well controlled and immune effector cell-associated neurotoxicity syndrome (ICANS) did not occur. This was the first case report of RV prepared anti-BCMA CAR-T cells combined with ASCT for the treatment of MM patient in clinical practice, indicating that the RV-based anti-BCMA-CAR-T cells with ASCT have excellent therapeutic efficacy and high safety in triple-refractory MM patients.

Comparison of hematopoietic stem cell transplantation and repeated intensified immunosuppressive therapy as second-line treatment for relapsed/refractory severe aplastic anemia.

The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7), or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.

Chinese guidelines for integrated diagnosis and treatment of intestinal microecology technologies in tumor application (2024 Edition).

ABSTRACT: Intestinal microecology (IM) is the largest and most important microecological system of the human body. Furthermore, it is the key factor for activating and maintaining the physiological functions of the intestine. Numerous studies have investigated the effects of the gut microbiota on the different tissues and organs of the human body as well as their association with various diseases, and the findings are gradually being translated into clinical practice. The gut microbiota affects the occurrence, progression, treatment response, and toxic side effects of tumors. The deepening of research related to IM and tumors has opened a new chapter in IM research driven by methods and technologies such as second-generation sequencing and bioinformatics. The IM maintains the function of the host immune system and plays a pivotal role in tumor-control drug therapy. Increasing evidence has proven that the efficacy of tumor-control drugs largely depends on the IM balance, and strategies based on the IM technology show promising application prospects in the diagnosis and treatment of tumor. The Tumor and Microecology Professional Committee of the Chinese Anti-cancer Association gathered relevant experts to discuss and propose the "Chinese guidelines for integrated diagnosis and treatment of IM technologies in tumor application (2024 Edition)," which was established based on the research progress of the application of the IM technology in tumor to provide a basis for the standardization of the diagnosis and treatment of the IM technology in the tumor.

KIF2A correlates with lymphovascular invasion and higher tumor stage, and can be used to predict worse prognosis in patients with endometrial carcinoma.

Kinesin family protein 2A (KIF2A) is a microtubule depolymerase that participates in the progression of various cancers; however, its clinical utility in endometrial carcinoma (EC) remains unclear. The aim of the present study was to assess KIF2A expression and its relationship with prognosis in patients with EC. Data from 230 patients with EC who underwent tumor resection were reviewed in the current, retrospective study. KIF2A expression was measured in 230 formalin-fixed paraffin-embedded (FFPE) specimens of tumor tissue and 50 FFPE specimens of non-tumor tissue using immunohistochemistry (IHC). KIF2A expression was elevated in EC tumor tissue vs. non-tumor tissue (P<0.001). Furthermore, tumor KIF2A expression was linked with lymphovascular invasion (P=0.004) and higher International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.001). High tumor KIF2A expression (IHC score>3) was correlated with shorter disease-free survival (DFS; P=0.014) and overall survival (OS; P=0.012). Moreover, the time-dependent receiver operating characteristic curves revealed that tumor KIF2A expression had an acceptable use for estimating the relapse and death risks at each timepoint within 6 years, with each area under the curve remaining stable at ≥0.7. Notably, tumor KIF2A expression (high vs. low) independently forecast shorter DFS (hazard ratio, 2.506; P=0.013), but not OS (P>0.05). Furthermore, information from The Human Protein Atlas database indicated that high tumor KIF2A expression was associated with worse OS in patients with EC (P=0.027). Tumor KIF2A is not only associated with lymphovascular invasion and higher FIGO stage, but also reflects unfavorable survival in patients with EC.

High PLK3 levels are linked with less tumor invasion, lower FIGO stage and better prognosis of endometrial cancer.

Aim: To evaluate correlations of tumor PLK3 with clinical features and prognosis of resectable endometrial cancer (EC) patients.Methods: Tumor tissues from 200 EC patients receiving surgical resections and adjacent tissues from 50 of them were collected for PLK3 determination using immunohistochemistry.Results: Tumor PLK3 negatively linked with myometrial invasion ≥50%, lymphovascular invasion, stromal cervical invasion, and International Federation of Gynecology and Obstetrics stage (all p < 0.050). High tumor PLK3 independently related to longer disease-free survival (DFS) (p = 0.044) and overall survival (OS) (p = 0.049). Its prognostic value was also validated by time-dependent receiver operating characteristic analyses (area under curve at most timepoints was >0.700).Conclusion: Tumor PLK3 potentially reflects prolonged DFS and OS in EC patients undergoing surgical resections.

[Box: see text].

The Drug-Drug Interaction between Erlotinib and OSI-930 Is Mediated through Aldehyde Oxidase Inhibition.

The propensity for aldehyde oxidase (AO) substrates to be implicated in drug-drug interactions (DDIs) is not well understood due to the dearth of potent inhibitors that elicit in vivo inhibition of AO. Although there is only one reported instance of DDI that has been ascribed to the inhibition of AO to date, the supporting evidence for this clinical interaction is rather tenuous, and its veracity has been called into question. Our group recently reported that the epidermal growth factor receptor inhibitor erlotinib engendered potent time-dependent inhibition of AO with inactivation kinetic constants in the same order of magnitude as its free circulating plasma concentrations. At the same time, it was previously reported that the concomitant administration of erlotinib with the investigational drug OSI-930 culminated in a an approximately twofold increase in its systemic exposure. Although the basis underpinning this interaction remains unclear, the structure of OSI-930 contains a quinoline motif that is amenable to oxidation at the electrophilic carbon adjacent to the nitrogen atom by molybdenum-containing hydroxylases like AO. In this study, we conducted metabolite identification that revealed that OSI-930 undergoes AO metabolism to a mono-oxygenated 2-oxo metabolite and assessed its formation kinetics in human liver cytosol. Additionally, reaction phenotyping in human hepatocytes revealed that AO contributes nearly 50% to the overall metabolism of OSI-930. Finally, modeling the interaction between erlotinib and OSI-930 using a mechanistic static model projected an ∼1.85-fold increase in the systemic exposure of OSI-930, which accurately recapitulated clinical observations. SIGNIFICANCE STATEMENT: This study delineates an aldehyde oxidase (AO) metabolic pathway in the investigational drug OSI-930 for the first time and confirmed that it represented a major route of metabolism through reaction phenotyping in human hepatocytes. Our study provided compelling mechanistic and modeling evidence for the first instance of an AO-mediated clinical drug-drug interaction stemming from the in vivo inhibition of the AO-mediated quinoline 2-oxidation pathway in OSI-930 by erlotinib.

Rapid response in relapsed follicular lymphoma to novel anti-CD19 CAR-T therapy with pseudo-progression and cytomegalovirus infection: A case report.

CD19-directed chimeric antigen receptor (CAR) T cell therapy has been shown to achieve a considerably durable response in patients with refractory or relapsed B cell non-Hodgkin lymphomas. Most of these CARs were generated by lentivirus. With the exception of Yescarta and Tecartus, few patients with relapsed-/refractory- lymphoma have been treated clinically with a CARs using retroviral vector (RV). Here, we reported a relapsed/refractory grade 2 follicular lymphoma patient with multiple chemotherapy failures, and was treated with a novel CD19 CAR-T cell manufactured from a RV. After tumor burden was reduced with Obinutuzumab and Duvelisib, the patient was infused novel CD19 CAR-T cells at a dose of 3 × 106 cells/ kg. Then he experienced a rapid response and achieved almost complete remission by day 26. Only grade 2 CRS, bilateral submaxillary lymph node enlargement and cytomegalovirus (CMV) infection occurred without neurotoxicity, and the patient's condition improved after a series of symptomatic treatments. In addition, CAR copy number peaked at 532,350 copies/µg on day 15 and continued to expand for 5 months. This may be the first case report of RV preparation of novel CD19 CAR-T cells for direct treatment of recurrent follicular lymphoma. We will observe its long-term efficacy and conduct trials in more patients in the future.

Oxygen Radical Coupling on Short-Range Ordered Ru Atom Arrays Enables Exceptional Activity and Stability for Acidic Water Oxidation.

The discovery of efficient and stable electrocatalysts for oxygen evolution reaction (OER) in acid is vital for the commercialization of the proton-exchange membrane water electrolyzer. In this work, we demonstrate that short-range Ru atom arrays with near-ideal Ru-Ru interatomic distances and a unique Ru-O hybridization state can trigger direct O*-O* radical coupling to form an intermediate O*-O*-Ru configuration during acidic OER without generating OOH* species. Further, the Ru atom arrays suppress the participation of lattice oxygen in the OER and the dissolution of active Ru. Benefiting from these advantages, the as-designed Ru array-Co3O4 electrocatalyst breaks the activity/stability trade-off that plagues RuO2-based electrocatalysts, delivering an excellent OER overpotential of only 160 mV at 10 mA cm-2 in 0.5 M H2SO4 and outstanding durability during 1500 h operation, representing one of the best acid-stable OER electrocatalysts reported to date. 18O-labeled operando spectroscopic measurements together with theoretical investigations revealed that the short-range Ru atom arrays switched on an oxide path mechanism (OPM) during the OER. Our work not only guides the design of improved acidic OER catalysts but also encourages the pursuit of short-range metal atom array-based electrocatalysts for other electrocatalytic reactions.

Interface stress transfer model and modulus parameter equivalence method for composite materials embedded with tensile pre-strain shape memory alloy fibers.

The constitutive model and modulus parameter equivalence of shape memory alloy composites (SMAC) serve as the foundation for the structural dynamic modeling of composite materials, which has a direct impact on the dynamic characteristics and modeling accuracy of SMAC. This article proposes a homogenization method for SMA composites considering interfacial phases, models the interface stress transfer of three-phase cylinders physically, and derives the axial and shear stresses of SMA fiber phase, interfacial phase, and matrix phase mathematically. The homogenization method and stress expression were then used to determine the macroscopic effective modulus of SMAC as well as the stress characteristics of the fiber phase and interface phase of SMA. The findings demonstrate the significance of volume fraction and tensile pre-strain in stress transfer between the fiber phase and interface phase at high temperatures. The maximum axial stress in the fiber phase is 705.05 MPa when the SMA is fully austenitic and the pre-strain increases to 5%. At 10% volume fraction of SMA, the fiber phase's maximum axial stress can reach 1000 MPa. Ultimately, an experimental verification of the theoretical calculation method's accuracy for the effective modulus of SMAC lays the groundwork for the dynamic modeling of SMAC structures.

Extracellular vesicles derived from immune cells: Role in tumor therapy.

Extracellular vesicles (EVs), which have a lipid nano-sized structure, are known to contain the active components of parental cells and play a crucial role in intercellular communication. The progression and metastasis of tumors are influenced by EVs derived from immune cells, which can simultaneously stimulate and suppress immune responses. In the past few decades, there has been a considerable focus on EVs due to their potential in various areas such as the development of vaccines, delivering drugs, making engineered modifications, and serving as biomarkers for diagnosis and prognosis. This review focuses on the substance information present in EVs derived from innate and adaptive immune cells, their effects on the immune system, and their applications in cancer treatment. While there are still challenges to overcome, it is important to explore the composition of immune cells released vesicles and their potential therapeutic role in tumor therapy. The review also highlights the current limitations and future prospects in utilizing EVs for treatment purposes.

Proximal telomeric decompaction due to telomere shortening drives FOXC1-dependent myocardial senescence.

Telomeres, TTAGGGn DNA repeat sequences located at the ends of eukaryotic chromosomes, play a pivotal role in aging and are targets of DNA damage response. Although we and others have demonstrated presence of short telomeres in genetic cardiomyopathic and heart failure cardiomyocytes, little is known about the role of telomere lengths in cardiomyocyte. Here, we demonstrate that in heart failure patient cardiomyocytes, telomeres are shortened compared to healthy controls. We generated isogenic human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) with short telomeres (sTL-CMs) and normal telomeres (nTL-CMs) as model. Compared to nTL-CMs, short telomeres result in cardiac dysfunction and expression of senescent markers. Using Hi-C and RNASeq, we observe that short telomeres induced TAD insulation decrease near telomeric ends and this correlated with a transcription upregulation in sTL-CMs. FOXC1, a key transcription factor involved in early cardiogenesis, was upregulated in sTL-CMs and its protein levels were negatively correlated with telomere lengths in heart failure patients. Overexpression of FOXC1 induced hiPSC-CM aging, mitochondrial and contractile dysfunction; knockdown of FOXC1 rescued these phenotypes. Overall, the work presented demonstrate that increased chromatin accessibility due to telomere shortening resulted in the induction of FOXC1-dependent expression network responsible for contractile dysfunction and myocardial senescence.

Addition of ruxolitinib to standard graft-versus-host disease prophylaxis for allogeneic stem cell transplantation in aplastic anemia patients.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers rapid hematopoietic and immune reconstitution for aplastic anemia (AA). As a non-malignant disorder, attenuation of GVHD remains a clinical priority in AA patients. Our study sought to investigate the safety and efficacy of the prophylactic use of ruxolitinib in allogeneic HSCT. A total of 35 AA patients were retrospectively consecutively treated with allo-HSCT whereby ruxolitinib was added to the standard GVHD prophylaxis regimen (rux group). The addition of peri-transplant ruxolitinib did not impact the engraftment and graft function, while better recovery of CD4+ Tregs in the rux group was observed. Interestingly, the rux group demonstrated significantly lower incidence of bacterial/fungal infections (17.14% vs 45.71%). Compared to the control group, the rux group exhibited significantly lower incidence of moderate to severe aGVHD (17.1% vs 48.6%) with a trend toward lower severe aGVHD (8.6% vs 20%) and cGVHD (26.2 vs 38.3). The rux group also demonstrated a trend toward higher GVHD and failure-free survival (GFFS: 85.7% vs 68.6%) and lower TRM (2.9% vs 14.3%). Addition of ruxolitinib to standard GVHD prophylaxis regimen, thus, represents a safe and highly efficient method for the attenuation of GVHD with better outcome of allo-HSCT.

Associations between residential greenness and obesity phenotypes among adults in Southwest China.

BACKGROUND: Although exposure to greenness has generally benefited human metabolic health, the association between greenness exposure and metabolic obesity remains poorly studied. We aimed to investigate the associations between residential greenness and obesity phenotypes and the mediation effects of air pollutants and physical activity (PA) level on the associations. METHODS: We used the baseline of the China Multi-Ethnic Cohort (CMEC) study, which enrolled 87,613 adults. Obesity phenotypes were defined based on obesity and metabolic status, including metabolically unhealthy obesity (MUO), non-obesity (MUNO), metabolically healthy obesity (MHO), and non-obesity (MHNO). Greenness exposure was measured as the 3-year mean values of the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) within the 500-m buffer zones around the participants' residence. Multivariable logistic regression was used to estimate the associations between greenness and obesity phenotypes. Stratified analyses by age, sex, educational level, and urbanicity were performed to identify how the effect varies across different subgroups. Causal mediation analysis was used to examine the mediation effects of air pollutants and PA level. RESULTS: Compared with MHNO, each interquartile range (IQR) increase in greenness exposure was associated with reduced risks of MHO (ORNDVI [95% CI] = 0.87 [0.81, 0.93]; OREVI = 0.91 [0.86, 0.97]), MUO (ORNDVI = 0.83 [0.78, 0.88]; OREVI = 0.86 [0.81, 0.91]), and MUNO (ORNDVI = 0.88 [0.84, 0.91]; OREVI = 0.89 [0.86, 0.92]). For each IQR increase in both NDVI and EVI, the risks of MHO, MUO, and MUNO were reduced more in men, participants over 60 years, those with a higher level of education, and those living in urban areas, compared to their counterparts. Concentrations of particulate matter (PM) and PA level partially mediated the associations between greenness exposure and obesity phenotypes. CONCLUSIONS: Exposure to residential greenness was associated with decreased risks of MHO, MUO, and MUNO, which was mediated by concentrations of PM and PA level, and modified by sex, age, educational level, and urbanicity.

Engineering Streptomyces sp. CPCC 204095 for the targeted high-level production of isatropolone A by elucidating its pathway-specific regulatory mechanism.

BACKGROUND: Isatropolone A and C, produced by Streptomyces sp. CPCC 204095, belong to an unusual class of non-benzenoid aromatic compounds and contain a rare seven-membered ring structure. Isatropolone A exhibits potent activity against Leishmania donovani, comparable to the only oral drug miltefosine. However, its variably low productivity represents a limitation for this lead compound in the future development of new anti-leishmaniasis drugs to meet unmet clinical needs. RESULTS: Here we first elucidated the regulatory cascade of biosynthesis of isatropolones, which consists of two SARP family regulators, IsaF and IsaJ. Through a series of in vivo and in vitro experiments, IsaF was identified as a pathway-specific activator that orchestrates the transcription of the gene cluster essential for isatropolone biosynthesis. Interestingly, IsaJ was found to only upregulate the expression of the cytochrome P450 monooxygenase IsaS, which is crucial for the yield and proportion of isatropolone A and C. Through targeted gene deletions of isaJ or isaS, we effectively impeded the conversion of isatropolone A to C. Concurrently, the facilitation of isaF overexpression governed by selected promoters, prompted the comprehensive activation of the production of isatropolone A. Furthermore, meticulous optimization of the fermentation parameters was conducted. These strategies culminated in the attainment of an unprecedented maximum yield-980.8 mg/L of isatropolone A-achieved in small-scale solid-state fermentation utilizing the genetically modified strains, thereby establishing the highest reported titer to date. CONCLUSION: In Streptomyces sp. CPCC 204095, the production of isatropolone A and C is modulated by the SARP regulators IsaF and IsaJ. IsaF serves as a master pathway-specific regulator for the production of isatropolones. IsaJ, on the other hand, only dictates the transcription of IsaS, the enzyme responsible for the conversion of isatropolone A and C. By engineering the expression of these pivotal genes, we have devised a strategy for genetic modification aimed at the selective and high-yield biosynthesis of isatropolone A. This study not only unveils the unique regulatory mechanisms governing isatropolone biosynthesis for the first time, but also establishes an essential engineering framework for the targeted high-level production of isatropolone A.

Advances in tumor vascular growth inhibition.

Tumor growth and metastasis require neovascularization, which is dependent on a complex array of factors, such as the production of various pro-angiogenic factors by tumor cells, intercellular signaling, and stromal remodeling. The hypoxic, acidic tumor microenvironment is not only conducive to tumor cell proliferation, but also disrupts the equilibrium of angiogenic factors, leading to vascular heterogeneity, which further promotes tumor development and metastasis. Anti-angiogenic strategies to inhibit tumor angiogenesis has, therefore, become an important focus for anti-tumor therapy. The traditional approach involves the use of anti-angiogenic drugs to inhibit tumor neovascularization by targeting upstream and downstream angiogenesis-related pathways or pro-angiogenic factors, thereby inhibiting tumor growth and metastasis. This review explores the mechanisms involved in tumor angiogenesis and summarizes currently used anti-angiogenic drugs, including monoclonal antibody, and small-molecule inhibitors, as well as the progress and challenges associated with their use in anti-tumor therapy. It also outlines the opportunities and challenges of treating tumors using more advanced anti-angiogenic strategies, such as immunotherapy and nanomaterials.

Case report: A case of hyperthyroidism secondary to bone metastasis of differentiated thyroid cancer.

It is usually believed that differentiated thyroid cancer is less likely to have distant metastases and rarely occurs secondary to hyperthyroidism. In our case report, we describe a patient diagnosed with thyroid fetal adenoma in 2002 who subsequently presented with a painful lump in her right rib. Through puncture biopsy, the mass was considered as metastatic follicular thyroid carcinoma, and then she appeared to have hyperthyroidism. The results of SPECT examination and other tests suggested that the hyperthyroidism was secondary to the thyroid cancer. The patient further underwent total thyroidectomy, and the pathology did not find any follicular thyroid foci. In this article, we analyze and discuss this case and review the relevant literature.

Cross-cultural perception of strength, attractiveness, aggressiveness and helpfulness of Maasai male faces calibrated to handgrip strength.

Previous research has demonstrated that Maasai and Europeans tend to align in their ratings of the physical strength and aggressiveness of Maasai male faces, calibrated to hand grip strength (HGS). However, perceptions of attractiveness of these faces differed among populations. In this study, three morphs of young Maasai men created by means of geometric morphometrics, and depicting the average sample and two extrema (± 4 SD of HGS), were assessed by men and women from Tanzania, Czech Republic, Russia, Pakistan, China, and Mexico (total sample = 1540). The aim of this study was to test cross-cultural differences in the perception of young Maasai men's composites calibrated to HGS, focusing on four traits: physical strength, attractiveness, aggressiveness, and helpfulness. Individuals from all six cultures were able to distinguish between low, medium, and high HGS portraits. Across all study populations, portrait of Maasai men with lower HGS was perceived as less attractive, more aggressive, and less helpful. This suggests that people from diverse populations share similar perceptions of physical strength based on facial shape, as well as attribute similar social qualities like aggressiveness and helpfulness to these facial images. Participants from all samples rated the composite image of weak Maasai men as the least attractive.

Nitrous oxide induced subacute combined degeneration of the spine cord: A case report.

RATIONALE: In recent years, recreational use of inhaled nitrous oxide (N2O) is on the increase among young people, accompanied by a corresponding rise in reports about its toxicity. Subacute combined degeneration of the spine cord (SCD) is the typical clinical picture of the nervous system disorder caused by N2O intoxication, as a result of metabolic disturbance of vitamin B12. PATIENT CONCERNS, DIAGNOSES, INTERVENTIONS AND OUTCOMES: We report a 28-year-old female of SCD due to prolonged use of N2O, presented with paresthesia and unsteady in walking progressing within 1 month. Symptoms gradually improved with the treatment of intramuscular injections of hydroxocobalamin combined with N2O abstinence, and the patient recovered completely with normal neurological examination after 4 months of follow-up. LESSONS: Clinicians should be aware of the clinical features and pathogenesis of SCD caused by N2O intoxication in order to lead effective treatment as soon as possible. Recreational N2O use should always be considered as an etiology when dealing with patients presented with myelopathy and/or neuropathy suspected of vitamin B12 deficiency.

Preliminary study on early diagnosis of Alzheimer's disease in APP/PS1 transgenic mice using multimodal magnetic resonance imaging.

Alzheimer's disease (AD) has an insidious onset and lacks clear early diagnostic markers, and by the time overt dementia symptoms appear, the disease is already in the mid-to-late stages. The search for early diagnostic markers of AD may open a critical window for Alzheimer's treatment and facilitate early intervention to slow the progression of AD. In this study, we aimed to explore the imaging markers for early diagnosis of AD through the combined application of structural magnetic resonance imaging (sMRI), resting-state functional magnetic resonance imaging (rs-fMRI), and 1H-magnetic resonance spectroscopy (1H-MRS) multimodal magnetic resonance imaging (MRI) techniques at the animal experimental level, with the aim to provide a certain reference for early clinical diagnosis of AD. First, sMRI scans were performed on 4-month-old amyloid beta precursor protein/presenilin 1 (APP/PS1) transgenic AD model mice and wild type mice of the same litter using a 7.0 T animal MRI scanner to analyze the differential brain regions with structural changes in the gray matter of the brain by voxel-based morphometry (VBM). Next, rs-fMRI scans were performed to analyze the differential brain regions between groups for local spontaneous brain activity and functional connectivity (FC) between brain regions. Finally, 1H-MRS scans were performed to quantify and analyze intergroup differences in the relative concentrations of different metabolites within regions of interest (cortex and hippocampus). Compared with wild type mice, the volume of the left hippocampus, and right olfactory bulb of APP/PS1 transgenic AD model mice were reduced, the functional activity of the bilateral hippocampus, right piriform cortex and right caudate putamen was reduced, the functional network connectivity of the hippocampus was impaired, and the relative content of N-acetylaspartate (NAA)in the hippocampus was decreased. In addition, this study found that imaging changes in olfactory-related brain regions were closely associated with AD diagnosis, and these findings may provide some reference for the early diagnosis of AD.