Effects of buccal acupuncture on postoperative analgesia in elderly patients undergoing laparoscopic radical gastrectomy: a randomized controlled trial.

Objective: This study aimed to evaluate the efficacy and safety of buccal acupuncture on postoperative analgesia, perioperative stress response and adverse events in elderly patients undergoing laparoscopic radical gastrectomy. Methods: It was a prospective, outcome assessor-blinded, randomized controlled trial, involving 90 patients aged 65-80 years who were treated with an elective laparoscopic radical gastrectomy. They were randomly assigned to buccal acupuncture group (Group B) and control group (Group C). Buccal acupuncture was applied to patients of Group B before the induction of general anesthesia, while no additional application was given to those in Group C. Patient-controlled intravenous analgesia (PCIA) with sufentanil was postoperatively performed in both groups. Sufentanil consumption and the Visual Analog Scale (VAS) score within 48 h postoperatively were assessed as primary outcomes. Secondary outcomes included peripheral levels of stress markers, intraoperative consumptions of anesthetic drugs and postoperative recovery. Results: Patients in Group B presented significantly lower VAS scores within 24 h and less consumption of sufentanil within 48 h postoperatively (both p < 0.01). The awaking time, time to extubation and length of stay were significantly shorter in Group B than in Group C (p = 0.005, 0.001 and 0.028, respectively). Compared with Group C, stress response and inflammatory response within 24 h postoperatively were also significantly milder in Group B. Conclusion: The use of buccal acupuncture before general anesthesia induction favors the postoperative analgesic effect and recovery in elderly patients undergoing laparoscopic radical gastrectomy, the mechanism of which involves relieving postoperative stress response and inflammatory response. Clinical trial registration: This study was registered in the Chinese Clinical Trial Registry (www.chictr.org.cn) on 15/06/2023 (ChiCTR2300072500).

The utility of methylmalonic acid, methylcitrate acid, and homocysteine in dried blood spots for therapeutic monitoring of three inherited metabolic diseases.

Backgroud: Routine metabolic assessments for methylmalonic acidemia (MMA), propionic acidemia (PA), and homocysteinemia involve detecting metabolites in dried blood spots (DBS) and analyzing specific biomarkers in serum and urine. This study aimed to establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous detection of three specific biomarkers (methylmalonic acid, methylcitric acid, and homocysteine) in DBS, as well as to appraise the applicability of these three DBS metabolites in monitoring patients with MMA, PA, and homocysteinemia during follow-up. Methods: A total of 140 healthy controls and 228 participants were enrolled, including 205 patients with MMA, 17 patients with PA, and 6 patients with homocysteinemia. Clinical data and DBS samples were collected during follow-up visits. Results: The reference ranges (25th-95th percentile) for DBS methylmalonic acid, methylcitric acid, and homocysteine were estimated as 0.04-1.02 µmol/L, 0.02-0.27 µmol/L and 1.05-8.22 µmol/L, respectively. Following treatment, some patients achieved normal metabolite concentrations, but the majority still exhibited characteristic biochemical patterns. The concentrations of methylmalonic acid, methylcitric acid, and homocysteine in DBS showed positive correlations with urine methylmalonic acid (r = 0.849, p < 0.001), urine methylcitric acid (r = 0.693, p < 0.001), and serum homocysteine (r = 0.721, p < 0.001) concentrations, respectively. Additionally, higher levels of DBS methylmalonic acid and methylcitric acid may be associated with increased cumulative complication scores. Conclusion: The LC-MS/MS method established in this study reliably detects methylmalonic acid, methylcitric acid, and homocysteine in DBS. These three DBS metabolites can be valuable for monitoring patients with MMA, PA, and homocysteinemia during follow-up. Further investigation is required to determine the significance of these DBS biomarkers in assessing disease burden over time.

Engineering Sonosensitizer-Derived Nanotheranostics for Augmented Sonodynamic Therapy.

Sonodynamic therapy (SDT), featuring noninvasive, deeper penetration, low cost, and repeatability, is a promising therapy approach for deep-seated tumors. However, the general or only utilization of SDT shows low efficiency and unsatisfactory treatment outcomes due to the complicated tumor microenvironment (TME) and SDT process. To circumvent the issues, three feasible approaches for enhancing SDT-based therapeutic effects, including sonosensitizer optimization, strategies for conquering hypoxia TME, and combinational therapy are summarized, with a particular focus on the combination therapy of SDT with other therapy modalities, including chemodynamic therapy, photodynamic therapy, photothermal therapy, chemotherapy, starvation therapy, gas therapy, and immunotherapy. In the end, the current challenges in SDT-based therapy on tumors are discussed and feasible approaches for enhanced therapeutic effects are provided. It is envisioned that this review will provide new insight into the strategic design of high-efficiency sonosensitizer-derived nanotheranostics, thereby augmenting SDT and accelerating the potential clinical transformation.

Research progress of microRNA in spinal cord injury.

Spinal cord injury (SCI) is a serious central nervous system disease with high disability and mortality rates and complex pathophysiologic mechanisms. MicroRNA (miRNA), as a kind of non-coding RNA, plays an important role in SCI. miRNA is involved in the regulation of inflammatory response, oxidative stress, axonal regeneration, and apoptosis after SCI, and interacts with long non-coding RNA (lncRNA) and circular RNA (circRNA) to regulate the pathophysiological process of SCI. This paper summarizes the changes in miRNA expression after SCI, and reviews the targeting mechanism of miRNA in SCI and the current research status of miRNA-targeted drugs to provide new targets and new horizons for basic and clinical research on SCI.

Clinical features and ALDH5A1 gene findings in 13 Chinese cases with succinic semialdehyde dehydrogenase deficiency.

BACKGROUND AND AIMS: To investigate the clinical features, ALDH5A1 gene variations, treatment, and prognosis of patients with succinic semialdehyde dehydrogenase (SSADH) deficiency. MATERIALS AND METHODS: This retrospective study evaluated the findings in 13 Chinese patients with SSADH deficiency admitted to the Pediatric Department of Peking University First Hospital from September 2013 to September 2023. RESULTS: Thirteen patients (seven male and six female patients; two sibling sisters) had the symptoms aged from 1 month to 1 year. Their urine 4-hydroxybutyrate acid levels were elevated and were accompanied by mildly increased serum lactate levels. Brain magnetic resonance imaging (MRI) showed symmetric abnormal signals in both sides of the globus pallidus and other areas. All 13 patients had psychomotor retardation, with seven showing epileptic seizures. Among the 18 variants of the ALDH5A1 gene identified in these 13 patients, six were previously reported, while 12 were novel variants. Among the 12 novel variants, three (c.85_116del, c.206_222dup, c.762C > G) were pathogenic variants; five (c.427delA, c.515G > A, c.637C > T, c.755G > T, c.1274T > C) were likely pathogenic; and the remaining four (c.454G > C, c.479C > T, c.1480G > A, c.1501G > C) were variants of uncertain significance. The patients received drugs such as L-carnitine, vigabatrin, and taurine, along with symptomatic treatment. Their urine 4-hydroxybutyric acid levels showed variable degrees of reduction. CONCLUSIONS: A cohort of 13 cases with early-onset SSADH deficiency was analyzed. Onset of symptoms occurred from 1 month to 1 year of age. Twelve novel variants of the ALDH5A1 gene were identified.

Helicobacter Pylori-Enhanced hnRNPA2B1 Coordinates with PABPC1 to Promote Non-m6A Translation and Gastric Cancer Progression.

Helicobacter pylori (H. pylori) infection is the primary risk factor for the pathogenesis of gastric cancer (GC). N6-methyladenosine (m6A) plays pivotal roles in mRNA metabolism and hnRNPA2B1 as an m6A reader is shown to exert m6A-dependent mRNA stabilization in cancer. This study aims to explore the role of hnRNPA2B1 in H. pylori-associated GC and its novel molecular mechanism. Multiple datasets and tissue microarray are utilized for assessing hnRNPA2B1 expression in response to H. pylori infection and its clinical prognosis in patients with GC. The roles of hnRNPA2B1 are investigated through a variety of techniques including glucose metabolism analysis, m6A-epitranscriptomic microarray, Ribo-seq, polysome profiling, RIP-seq. In addition, hnRNPA2B1 interaction with poly(A) binding protein cytoplasmic 1 (PABPC1) is validated using mass spectrometry and co-IP. These results show that hnRNPA2B1 is upregulated in GC and correlated with poor prognosis. H. pylori infection induces hnRNPA2B1 upregulation through recruiting NF-κB to its promoter. Intriguingly, cytoplasm-anchored hnRNPA2B1 coordinated PABPC1 to stabilize its relationship with cap-binding eIF4F complex, which facilitated the translation of CIP2A, DLAT and GPX1 independent of m6A modification. In summary, hnRNPA2B1 facilitates the non-m6A translation of epigenetic mRNAs in GC progression by interacting with PABPC1-eIF4F complex and predicts poor prognosis for patients with GC.

Constructing hierarchical CuS hollow spheres as efficient anode for aqueous zinc-ion batteries.

In recent years, aqueous zinc-ion batteries (ZIBs) have emerged as a prominent research topic due to their inherent safety attributes, relatively low cost, and comparatively higher energy density. However, the challenges associated with the zinc metal anode in the form of dendrite formation, hydrogen evolution, and severe side reactions have proven to be particularly vexing. Thus, it is imperative to investigate novel intercalation-type anode materials for ZIBs that exhibit exceptional structural properties and appropriate redox potentials based on conversion mechanisms. In this work, through adding polyvinylpyrrolidone (PVP) surfactant to precursors and tailoring reaction time, hierarchical CuS hollow spheres are successfully constructed by a facile one-step hydrothermal process. When applied as an anode in ZIBs, the hollow hierarchical CuS with large surface area can effectively reduce the transport distance of electrons and Zn2+ and alleviate volume expansion during the insertion/extraction of Zn2+. The hierarchical CuS hollow spheres prepared over 8 h (CuS-8) exhibit a specific capacity of 126 mAh/g and long-term cycle life (1500 cycles) at a current density of 3 A/g. In addition, CuS-8//MnO2@CNTs full-cell shows a capacity retention of 117 mAh/g after 300 cycles at 1 A/g current density, which proves the advantage of hierarchical CuS hollow spheres in serving as an efficient and durable anode material for ZIBs.

Indiscriminate activities of different henipavirus polymerase complex proteins allow for efficient minigenome replication in hybrid systems.

The henipaviruses, including Nipah virus (NiV) and Hendra virus (HeV), are biosafety level 4 (BSL-4) zoonotic pathogens that cause severe neurological and respiratory disease in humans. To study the replication machinery of these viruses, we developed robust minigenome systems that can be safely used in BSL-2 conditions. The nucleocapsid (N), phosphoprotein (P), and large protein (L) of henipaviruses are critical elements of their replication machinery and thus essential support components of the minigenome systems. Here, we tested the effects of diverse combinations of the replication support proteins on the replication capacity of the NiV and HeV minigenomes by exchanging the helper plasmids coding for these proteins among the two viruses. We demonstrate that all combinations including one or more heterologous proteins were capable of replicating both the NiV and HeV minigenomes. Sequence alignment showed identities of 92% for the N protein, 67% for P, and 87% for L. Notably, variations in amino acid residues were not concentrated in the N-P and P-L interacting regions implying that dissimilarities in amino acid composition among NiV and HeV polymerase complex proteins may not impact their interactions. The observed indiscriminate activity of NiV and HeV polymerase complex proteins is different from related viruses, which can support the replication of heterologous genomes only when the whole polymerase complex belongs to the same virus. This newly observed promiscuous property of the henipavirus polymerase complex proteins likely attributed to their conserved interaction regions could potentially be harnessed to develop universal anti-henipavirus antivirals.IMPORTANCEGiven the severity of disease induced by Hendra and Nipah viruses in humans and the continuous emergence of new henipaviruses as well as henipa-like viruses, it is necessary to conduct a more comprehensive investigation of the biology of henipaviruses and their interaction with the host. The replication of henipaviruses and the development of antiviral agents can be studied in systems that allow experiments to be performed under biosafety level 2 conditions. Here, we developed robust minigenome systems for the Nipah virus (NiV) and Hendra virus (HeV) that provide a convenient alternative for studying NiV and HeV replication. Using these systems, we demonstrate that any combination of the three polymerase complex proteins of NiV and HeV could effectively initiate the replication of both viral minigenomes, which suggests that the interaction regions of the polymerase complex proteins could be effective targets for universal and effective anti-henipavirus interventions.

Loss-of-function mutation in DDX53 associated with hereditary spastic paraplegia-like disorder.

DEAD-box helicase 53 (DDX53) is a member of the DEAD-box protein family of RNA helicases. Unlike other family members that are responsible for RNA metabolism, the biological function of DDX53 and its impact on the human condition are unclear. Herein, we found a full-length DDX53 deletion mutation in a hereditary spastic paraplegia-like (HSP-like) patient with lower extremity spasticity, walking disorder, visual impairment, and lateral ventricular white matter lesions. Bioinformatic analysis revealed that DDX53 was mainly expressed in the cerebellar cortex and may function as a tissue-specific RNA helicase. Transcriptome analysis showed that the expression of multiple brain-associated genes involved in synapse organization, neuron function, and neuromuscular junctions was affected by DDX53 depletion. Moreover, RNA immunoprecipitation sequencing (RIP-seq) analysis showed that DDX53 interacted with 176 genes, and 96 of these genes were associated with the execution of neurofunction, particularly in the regulation of cell projection organization and nervous system development. Collectively, although a more specified cell or animal model is required to fully understand the functional role of DDX53 in the human brain, we report for the first time that the patient with DDX53 defects exhibits HSP-like symptoms and that DDX53 is essential for maintaining neuronal function, with loss-of-function mutation in DDX53 potentially leading to HSP due to impaired RNA metabolism in the nervous system. KEY MESSAGES: DDX53 deficiency was first reported to be associated with HSP disorder. DDX53 exhibited minimal impact on mitochondrial function. DDX53 impaired RNA metabolism in the nervous system.

CircUGGT2 downregulation by METTL14-dependent m6A modification suppresses gastric cancer progression and cisplatin resistance through interaction with miR-186-3p/MAP3K9 axis.

Chemoresistance is a major therapeutic challenge in advanced gastric cancer (GC). N6-methyladenosine (m6A) RNA modification has been shown to play fundamental roles in cancer progression. However, the underlying mechanisms by which m6A modification of circRNAs contributes to GC and chemoresistance remain unknown. We found that hsa_circ_0030632 (circUGGT2) was a predominant m6A target of METTL14, and METTL14 knockdown (KD) reduced circUGGT2 m6A levels but increased its mRNA levels. The expression of circUGGT2 was markedly increased in cisplatin (DDP)-resistant GC cells. CircUGGT2 KD impaired cell growth, metastasis and DDP-resistance in vitro and in vivo, but circUGGT2 overexpression prompted these effects. Furthermore, circUGGT2 was validated to sponge miR-186-3p and upregulate MAP3K9 and could abolish METTL14-caused miR-186-3p upregulation and MAP3K9 downregulation in GC cells. circUGGT2 negatively correlated with miR-186-3p expression and harbored a poor prognosis in patients with GC. Our findings unveil that METTL14-dependent m6A modification of circUGGT2 inhibits GC progression and DDP resistance by regulating miR-186-3p/MAP3K9 axis.

Results of a Pilot External Quality Assessment Scheme for Genetic Testing of Newborns with Spinal Muscular Atrophy.

BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Association between sleep duration and serum neurofilament light chain levels among adults in the United States.

Background: Neurofilaments are neuron specific skeleton proteins maintaining axon transduction speed, leaked into cerebrospinal fluid and serum after axonal injury or neuron death. Sleep duration change has long related to many health issues but lack laboratory examination. Methods: This study enrolled total 10,175 participants from 2013 to 2014 National Health and Nutrition Examination Survey and used a multi-variable linear model to analyze the relationship between sleep duration and serum neurofilament light chain (sNfL) level. Results: There was a fixed relationship between sleep duration and sNfL level (ß = 0.65, p = 0.0280). After adjusted for covariates, this relationship still (ß = 0.82, p = 0.0052). Segmented regression showed that the turning point of sleep duration was 7 h 1 h decrease in sleep duration was significantly associated with -1.26 higher sNfL level (95 % CI: 2.25, -0.28; p = 0.0115) when sleep duration <7 h; however, 1 h increase in sleep duration was significantly associated with 3.20 higher sNfL level (95 % CI: 2.13, 4.27; p < 0.0001) when sleep duration >7 h. Furthermore, the stratified analysis indicated that the associations between sleep duration and sNfL level were stronger among those normal body mass index and trouble sleeping (p-interaction <0.0001 and 0.0003). Conclusion: In summary, there was a J-shaped relationship between sleep duration and sNfL level in the United States of America representative group, these may suggest that extreme sleep duration can be deleterious judged by sNfL level. And still need large cohort study to determine the accurate relationship, and cluster analysis to infer the nervous disease connected with extreme sleep duration.

Constructing hierarchical MoS2/WS2 heterostructures in dual carbon layer for enhanced sodium ions batteries performance.

The escalating global demand for clean energy has spurred substantial interest in sodium-ion batteries (SIBs) as a promising solution for large-scale energy storage systems. However, the insufficient reaction kinetics and considerable volume changes inherent to anode materials present significant hurdles to enhancing the electrochemical performance of SIBs. In this study, hierarchical MoS2/WS2 heterostructures were constructed into dual carbon layers (HC@MoS2/WS2@NC) and assessed their suitability as anodes for SIBs. The internal hard carbon core (HC) and outer nitrogen-doped carbon shell (NC) effectively anchor MoS2/WS2, thereby significantly improving its structural stability. Moreover, the conductive carbon components expedite electron transport during charge-discharge processes. Critically, the intelligently engineered interface between MoS2 and WS2 modulates the interfacial energy barrier and electric field distribution, promoting faster ion transport rates. Capitalizing on these advantageous features, the HC@MoS2/WS2@NC nanocomposite exhibits outstanding electrochemical performance when utilized as an anode in SIBs. Specifically, it delivers a high capacity of 415 mAh/g at a current density of 0.2 A/g after 100 cycles. At a larger current density of 2 A/g, it maintains a commendable capacity of 333 mAh/g even after 1000 cycles. Additionally, when integrated into a full battery configuration with a Na3V2(PO4)3 cathode, the Na3V2(PO4)3//HC@MoS2/WS2@NC full cell delivers a high capacity of 120 mAh/g after 300 cycles at 1 A/g. This work emphasizes the substantial improvement in battery performance that can be attained through the implementation of dual carbon confinement, offering a constructive approach to guide the design and development of next-generation anode materials for SIBs.

Design and synthesis of sulfonamide phenothiazine derivatives as novel ferroptosis inhibitors and their therapeutic effects in spinal cord injury.

Ferroptosis is a novel style of cell death, and studies have shown that ferroptosis is strongly associated with spinal cord injury (SCI). A large number of ferroptosis inhibitors have been reported, but so far no ferroptosis inhibitor has been used clinically. Therefore there is an urgent need to discover a better inhibitor of ferroptosis. In this study, 24 novel sulfonamide phenothiazine ferroptosis inhibitors were designed and synthesized, followed by structure-activity relationship studies on these compounds. Among them, compound 23b exhibited the best activity in Erastin-induced PC12 cells (EC50 = 0.001 µM) and demonstrated a low hERG inhibition activity (IC50 > 30 µM). Additionally, compound 23b was identified as a ROS scavenger and showed promising therapeutic effects in an SD rat model of SCI. Importantly, 23b did not display significant toxicity in both in vivo and in vitro experiments and show good pharmacokinetic properties. These findings suggest that compound 23b, a novel ferroptosis inhibitor, holds potential as a therapeutic agent for spinal cord injury and warrants further investigation.

From bench to bedside: Overview of magnetoencephalography in basic principle, signal processing, source localization and clinical applications.

Magnetoencephalography (MEG) is a non-invasive technique that can precisely capture the dynamic spatiotemporal patterns of the brain by measuring the magnetic fields arising from neuronal activity along the order of milliseconds. Observations of brain dynamics have been used in cognitive neuroscience, the diagnosis of neurological diseases, and the brain-computer interface (BCI). In this study, we outline the basic principle, signal processing, and source localization of MEG, and describe its clinical applications for cognitive assessment, the diagnoses of neurological diseases and mental disorders, preoperative evaluation, and the BCI. This review not only provides an overall perspective of MEG, ranging from practical techniques to clinical applications, but also enhances the prevalent understanding of neural mechanisms. The use of MEG is expected to lead to significant breakthroughs in neuroscience.

Micro-computed tomographic evaluation on the quality of single-cone obturation using a modified passive-deflation sealer injection needle: an in vitro study.

OBJECTIVES: This study aimed to design a modified passive-deflation sealer injection needle and investigate its ability to improve obturation quality of single-cone technique through assessing the distribution of voids in root canals using micro-computed tomography (micro-CT). MATERIALS AND METHODS: Forty-eight mandibular incisors were divided into eight groups (n = 6), according to the taper of root canal preparation (0.06 or 0.04), the needle used for sealer injection (modified or commercial iRoot SP injection needle), and the obturation method (iRoot SP sealer-only or single-cone obturation). After obturation, each specimen was scanned by micro-CT. The volumetric percentage and distribution of all voids were first analyzed and compared among groups, then the open and closed voids were separately analyzed and compared among single-cone obturation groups. RESULTS: Compared to commercial needle groups, modified needle groups showed much less voids, especially in the apical root canal part (P < 0.05). Besides, the modified needle groups produced much less open voids than commercial needle groups despite the root canal taper (P < 0.05). CONCLUSIONS: The modified passive deflation sealer injection needle could effectively improve the quality of single-cone obturation through reducing intra-canal voids, especially open voids throughout the root canal, thus might possibly be developed as an effective intra-canal sealer delivering instrument.

Dual rare genetic diseases in five pediatric patients: insights from next-generation diagnostic methods.

BACKGROUND: Clinicians traditionally aim to identify a singular explanation for the clinical presentation of a patient; however, in some cases, the diagnosis may remain elusive or fail to comprehensively explain the clinical findings. In recent years, advancements in next-generation sequencing, including whole-exome sequencing, have led to the incidental identification of dual diagnoses in patients. Herein we present the cases of five pediatric patients diagnosed with dual rare genetic diseases. Their natural history and diagnostic process were explored, and lessons learned from utilizing next-generation diagnostic technologies have been reported. RESULTS: Five pediatric cases (3 boys, 2 girls) with dual diagnoses were reported. The age at diagnosis was from 3 months to 10 years. The main clinical presentations were psychomotor retardation and increased muscular tension, some accompanied with liver dysfunction, abnormal appearance, precocious puberty, dorsiflexion restriction and varus of both feet, etc. After whole-exome sequencing, nine diseases were confirmed in these patients: Angelman syndrome and Krabbe disease in case 1, Citrin deficiency and Kabuki syndrome in case 2, Homocysteinemia type 2 and Copy number variant in case 3, Isolated methylmalonic acidemia and Niemann-Pick disease type B in case 4, Isolated methylmalonic acidemia and 21-hydroxylase deficiency in case 5. Fifteen gene mutations and 2 CNVs were identified. Four novel mutations were observed, including c.15292de1A in KMT2D, c.159_164inv and c.1427G > A in SLC25A13, and c.591 C > G in MTHFR. CONCLUSIONS: Our findings underscore the importance of clinicians being vigilant about the significance of historical and physical examination. Comprehensive clinical experience is crucial for identifying atypical clinical features, particularly in cases involving dual rare genetic diseases.

Haploidentical hematopoietic stem cell transplantation with busulfan, cyclophosphamide, and fludarabine conditioning for X-linked adrenal cerebral leukodystrophy.

OBJECTIVE: We investigated the safety and efficacy of haploidentical stem cell transplantation (SCT) in pediatric patients with X-linked adrenoleukodystrophy (ALD). METHODS: A retrospective analysis of transplantation data from 29 cases of ALD, treated between December 2014 and April 2022, was conducted. Neurologic function scores (NFS) were assessed. The conditioning regimen was busulfan 9.6 mg/kg, cyclophosphamide 200 mg/kg, and fludarabine 90 mg/m2 (BFC). Graft-versus-host disease prophylaxis consisted of anti-human thymocyte globulin, cyclosporine A, mycophenolate mofetil, and short course of methotrexate. RESULTS: Among the 29 cases, 14 cases (NFS = 0) were asymptomatic, and 15 (NFS ≥ 1) were symptomatic. The median age at SCT was 8 years (range: 4-16 years); the median follow-up time was 1058 days (range: 398-3092 days); 28 cases were father donors and 1 case was a grandfather donor. Hematopoietic reconstitution was successful in all patients, and all of them achieved complete donor chimerism at the time of engraftment. The leading cause of death was still primary disease progression (n = 4). Survival free of major functional disabilities was 100% in asymptomatic patients versus 66.67% in the symptomatic group (p = .018). CONCLUSION: BFC regimen used in haploidentical SCT was administered safely without major transplant-related complications even in symptomatic patients, and neurological symptoms were stabilized after SCT.

Result of a Pilot External Quality Assessment Scheme for Clinical Diagnosis of Inherited Metabolic Disorders in China.

BACKGROUND: We aimed to evaluate the diagnostic capabilities of Chinese laboratories for inherited metabolic disorders (IMDs) using gas chromatography-mass spectrometry (GC-MS) on urine samples. Meanwhile, based on the result of the pilot external quality assessment (EQA) scheme, we hope to establish a standardized and reliable procedure for future EQA practice. METHODS: We recruited laboratories that participated in the EQA of quantitative analysis of urinary organic acids with GC-MS before joining the surveys. In each survey, a set of five real urine samples was distributed to each participant. The participants should analyze the sample by GC-MS and report the "analytical result", "the most likely diagnosis", and "recommendation for further tests" to the NCCL before the deadline. RESULTS: A total of 21 laboratories participated in the scheme. The pass rates were 94.4% in 2020 and 89.5% in 2021. For all eight IMDs tested, the analytical proficiency rates ranged from 84.7% - 100%, and the interpretational performance rate ranged from 88.2% - 97.0%. The performance on hyperphenylalaninemia (HPA), 3-methylcrotonyl-CoA carboxylase deficiency (MCCD), and ethylmalonic encephalopathy (EE) samples were not satisfactory. CONCLUSIONS: In general, the participants of this pilot EQA scheme are equipped with the basic capability for qualitative organic acid analysis and interpretation of the results. Limited by the small size of laboratories and samples involved, this activity could not fully reflect the state of clinical practice of Chinese laboratories. NCCL will improve the EQA scheme and implement more EQA activities in the future.

Detachable string magnetically controlled capsule endoscopy for the noninvasive diagnosis of esophageal diseases: A prospective, blind clinical study.

BACKGROUND: Traditional esophagogastroduodenoscopy (EGD), an invasive examination method, can cause discomfort and pain in patients. In contrast, magnetically controlled capsule endoscopy (MCE), a noninvasive method, is being applied for the detection of stomach and small intestinal diseases, but its application in treating esophageal diseases is not widespread. AIM: To evaluate the safety and efficacy of detachable string MCE (ds-MCE) for the diagnosis of esophageal diseases. METHODS: Fifty patients who had been diagnosed with esophageal diseases were prospectively recruited for this clinical study and underwent ds-MCE and conventional EGD. The primary endpoints included the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of ds-MCE for patients with esophageal diseases. The secondary endpoints consisted of visualizing the esophageal and dentate lines, as well as the subjects' tolerance of the procedure. RESULTS: Using EGD as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of ds-MCE for esophageal disease detection were 85.71%, 86.21%, 81.82%, 89.29%, and 86%, respectively. ds-MCE was more comfortable and convenient than EGD was, with 80% of patients feeling that ds-MCE examination was very comfortable or comfortable and 50% of patients believing that detachable string v examination was very convenient. CONCLUSION: This study revealed that ds-MCE has the same diagnostic effects as traditional EGD for esophageal diseases and is more comfortable and convenient than EGD, providing a novel noninvasive method for treating esophageal diseases.