ObjectiveTo investigate the functional role and underlying molecular mechanisms of fumarylacetoacetate hydrolase （FAH） in the progression of glioblastoma （GBM）. MethodsDifferential expression analysis was performed on the TCGA-GBM， GSE4290， and GSE116520 datasets. Weighted gene co-expression network analysis （WGCNA） was used to identify key modules， and Cox regression and risk modeling were used to screen prognostic genes. Immune infiltration analysis of prognostic genes was carried out by using single-cell RNA sequencing panels. The clinical expression signature of FAH in GBM was analyzed in the TCGA and HPA databases. The functional role of FAH was validated by in vitro and in vivo experiments， and pathway analysis was performed to explore the underlying mechanisms. ResultsA total of 152 overlapping genes were identified across the three GBM datasets （P<0.05）. WGCNA revealed that the turquoise module was most strongly associated with tumor purity， stromal score， immune score， and ESTIMATE score （P<0.001）. Compared with normal tissues， three prognostic genes （CTSD， FAH， and THBD） were upregulated in GBM and correlated with immune infiltration （P<0.05）. FAH mRNA and protein levels were elevated in GBM tissues relative to normal tissues， and its expression was significantly associated with age stratification and TP53 mutation （P<0.05）. CCK-8 assay results showed that， compared with the shNC group， the proliferative activity of GBM cells in the shFAH group was reduced （P<0.001）. Transwell migration and invasion assays demonstrated that， relative to the shNC group， the numbers of migrated and invaded cells in the shFAH group decreased （P<0.05）. Western blot analysis revealed that the protein expression levels of PI3K， p-AKT， and p-mTOR in the shFAH group decreased compared with those in the shNC group （P<0.05）. In vivo subcutaneous xenograft experiments further confirmed that tumor volume and weight significantly decreased in the shFAH group compared with the shNC group （P<0.001）. ConclusionFAH promotes GBM progression by activating the PI3K/AKT/mTOR signaling pathway and may serve as a potential therapeutic target for GBM.

Objective To explore the clinical features, diagnosis, treatment and prognosis of testicular Ewing sarcoma(ES), so as to enhance the understanding and differential diagnosis of this disease. Methods A retrospective analysis was conducted on the clinical manifestations, auxiliary examinations and pathological findings of a case of left-sided ES treated at our hospital, supplemented by a review of relevant literature. Results A 24-year-old male patient presented with left testicular enlargement with pain. Magnetic resonance imaging suggested a neoplastic lesion, with a high likelihood of testicular germ cell tumor. A radical left orchiectomy was performed. Postoperative pathology revealed testicular ES. The patient subsequently completed 8 cycles of VDC/IE chemotherapy and showed no evidence of recurrence at 10 months of follow-up. Analysis of literature on 5 previously reported cases of testicular ES had testicular enlargement as the primary presentation. All patients underwent surgery and 4 received adjuvant therapy. Follow-up revealed 1 death at 9 months postoperatively, with no recurrence or progression seen in the remainder. Conclusion ES occurring in the testis is extremely rare.Testicular ES is a poorly differentiated small round-cell malignant tumor that primarily presents as testicular enlargement. Current treatment mainly surgical resection combined with adjuvant chemotherapy.

BackgroundObsessive-compulsive disorder （OCD） carries a considerable disability burden. Intolerance of uncertainty （IU） is associated with the severity of obsessive-compulsive symptoms， yet its neural underpinnings remain unclear. The cerebellum has been implicated in uncertainty processing and demonstrates structural and functional abnormalities in OCD， but direct evidence linking its spontaneous activity to the relationship between IU and obsessive-compulsive symptoms is still lacking. ObjectiveTo explore the pathway through which spontaneous cerebellar neural activity mediates the relationship between IU and obsessive-compulsive symptoms in OCD patients， with the aim of providing a new perspective for understanding the neural mechanisms of OCD. MethodsA total of 51 patients with OCD who visited the Mental Health Center outpatient clinic of the General Hospital of Ningxia Medical University from November 2022 to November 2024 and met the diagnostic criteria for OCD according to the International Classification of Diseases， tenth edition （ICD-10）. During the same period， 43 community-based volunteers matched for gender and age were enrolled as the control group. Resting-state functional magnetic resonance imaging data were collected from two groups. Amplitude of low-frequency fluctuation （ALFF） analysis was used to compare whole-brain spontaneous neural activity between two groups. Clinical assessments were conducted using the Yale-Brown Obsessive Compulsive Scale （Y-BOCS） and the Intolerance of Uncertainty Scale-12 （IUS-12）. Pearson correlation analysis was used to examine correlations between cerebellar ALFF values and scale scores in OCD patients. Using IU as the independent variable， obsessive-compulsive symptoms as the dependent variable， and ALFF values from between-group difference brain regions as the mediator， Process 4.0 for SPSS 24.0 （model 4） was used to examine the mediating role of these ALFF values between IU and obsessive-compulsive symptoms. The Bootstrap method was used to test the mediation effect. ResultsA total of 47 OCD patients and 40 controls completed this study. Compared with the control group， the OCD group showed decreased ALFF values in the right cerebellar Crus Ⅱ （t=-5.254， FWE-corrected P<0.01）. Correlation analysis revealed that ALFF value in the right cerebellar Crus Ⅱ was negatively correlated with Y-BOCS total score （r=-0.851）， compulsive behavior subscale score （r=-0.647）， IUS-12 total scores （r=-0.617）， and prospective IU subscale scores （r=-0.717） in OCD group （P<0.01）. Prospective IU subscale scores were positively correlated with Y-BOCS total scores （r=0.811） and compulsive behavior subscale score （r=0.535） （P<0.01）. Mediation analysis showed that ALFF value in the right cerebellar Crus Ⅱ region partially mediated the effect of prospective IU on obsessive-compulsive behavior， with a mediation effect of 0.064 （95% CI： 0.004–0.136）， accounting for 24.57% of the total effect. ConclusionPatients with OCD showed reduced spontaneous neural activity in the right cerebellar Crus Ⅱ region， which was significantly associated with IU and obsessive-compulsive symptoms. This region partially mediated the effect of IU on compulsive behaviors. ［Funded by Basic Conditions and Innovation Platform Construction Project of Ningxia Hui Autonomous Region in 2023 （number， 2022YXGCJS001）］

Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity, expanding antibacterial spectra, and reducing required dosages. Previously, compound 15 was identified as a potential adjuvant for Polymyxin B (PB) against multidrug-resistant (MDR) Pseudomonas aeruginosa DK2; however, its clinical utility was hindered by high cytotoxicity, uncertain in vivo efficacy, and an unclear synergetic mechanism. To address these challenges, we synthesized and evaluated a series of novel benzamide derivatives, with A22 emerging as a particularly promising candidate. A22 demonstrated potent synergistic activity to PB, minimal cytotoxicity, improved water solubility, and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains. In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22. Moreover, A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2. Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production, reducing ATP levels, increasing NOX activity, and inhibiting biofilm formation, leading to bacterial death. These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants, offering a robust approach to combating MDR Gram-negative bacterial infections.

OBJECTIVES: To investigate the role of ferroptosis in diquat-induced acute kidney injury (AKI) and its molecular mechanisms. METHODS: Transgenic zebrafish models with Tg (Eco.Tshb:EGFP) labeling of the renal tubules and Tg (lyz:dsRed2) labeling of the neutrophils were both divided into control group, gentamicin (positive control) group, diquat poisoning group, ferroptosis inhibitor group. The indicators of kidney injury, inflammatory response, and ferroptosis were examined in the zebrafish, and the changes in expressions of voltage-dependent anion-selective channel protein 1 (VDAC1) and mitochondrial ferritin (FTMT) were detected using Western blotting. RESULTS: AKI induced by diquat exhibited a significant dose-effect relationship, and the severity of injury was proportional to the exposure concentration. Diquat also caused marked oxidative stress and inflammatory responses in the zebrafish models. Rhodamine metabolism assay and HE staining revealed significantly declined glomerular filtration function of the zebrafish as diquat exposure concentration increased. Immunofluorescence staining highlighted significant changes in the expressions of ferroptosis markers GPX4 and FTH1 in zebrafish renal tissues following diquat exposure. In diquat-exposed zebrafish, treatment with ferrostatin-1, a ferroptosis inhibitor, obviously upregulated GPX4 and downregulated FTH1 expressions and improved the metabolic rate of glucan labeled with rhodamine B. Diquat exposure significantly upregulated the expression of VDAC1 and FTMT in zebrafish, and the application of ferrostatin-1 and VBIT-12 (a VDAC1 inhibitor) both caused pronounced downregulation of FTMT expression. CONCLUSIONS Ferroptosis is a critical mechanism underlying diquat-induced AKI, in which VDAC1 and FTMT play important regulatory roles, suggesting their potential as therapeutic target for AKI caused by diquat.
Animals ; Zebrafish ; Ferroptosis/drug effects* ; Acute Kidney Injury/chemically induced* ; Diquat/toxicity* ; Animals, Genetically Modified ; Voltage-Dependent Anion Channel 1/metabolism* ; Ferritins/metabolism* ; Oxidative Stress

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

Through collecting the existing clinical evidences on acupuncture and moxibustion for urticaria, the distribution of evidence in this field was mapped. A systematic search of Chinese and English literature was conducted in CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library for treatment of urticaria with acupuncture and moxibustion, published up to December 31, 2023 since inception of each database. The research status in this field was summarized using an evidence mapping approach, and methodological quality was assessed. A total of 323 randomized controlled trials (RCTs) and 22 systematic reviews were included. The number of studies on acupuncture and moxibustion for urticaria has been increasing, with a significant rise in recent years. In most RCTs, the study scale was small, and the subjects focused on chronic spontaneous urticaria in adolescents and middle-aged adults, aged 14 to 60 years. Regarding the intervention measures, the single therapy of acupuncture and moxibustion was predominant such as acupoint injection, acupoint embedding thread, and filiform needling. In acupuncture with filiform needles, the commonly used acupoints were Quchi (LI11), Xuehai (SP10), Sanyinjiao (SP6), Zusanli (ST36) and Hegu (LI4). The main outcome measures referred to effectiveness rate, score of disease severity, recurrence rate, laboratory indexes, and score of quality of life; and the short-term effect was evaluated specifically. The overall methodological quality of the included studies was relatively low. It is suggested that the future research should focus on large-scale, multi-center, high-quality clinical trials, optimize the protocols for acupuncture and moxibustion intervention, standardize the outcomes, and draw the attention to the evaluation of long-term efficacy, so as to provide clinical evidences of high certainty for urticaria treated with acupuncture and moxibustion.
Humans ; Moxibustion ; Acupuncture Therapy ; Urticaria/therapy* ; Acupuncture Points ; Randomized Controlled Trials as Topic ; Adolescent ; Adult ; Young Adult

Flexible conductive fibers have been widely applied in wearable flexible sensing. However, exposed wearable flexible sensors based on liquid metal (LM) are prone to abrasion and significant conductivity degradation. This study presented a high-sensitivity LM conductive fiber with integration of strain sensing, electrical heating, and thermochromic capabilities, which was fabricated by coating eutectic gallium-indium (EGaIn) onto spandex fibers modified with waterborne polyurethane (WPU), followed by thermal curing to form a protective polyurethane sheath. This fiber, designated as Spandex/WPU/EGaIn/Polyurethane (SWEP), exhibits a four-layer coaxial structure: spandex core, WPU modification layer, LM conductive layer, and polyurethane protective sheath. The SWEP fiber had a diameter of (458.3 ± 10.4) μm, linear density of (2.37 ± 0.15) g/m, and uniform EGaIn coating. The fiber had excellent conductivity with an average value of (3 716.9 ± 594.2) S/m. The strain sensing performance was particularly noteworthy. A 5 cm × 5 cm woven fabric was fabricated using polyester warp yarns and SWEP weft yarns. The fabric exhibited satisfactory moisture permeability [(536.06 ± 33.15) g/(m ²·h)] and maintained stable thermochromic performance after repeated heating cycles. This advanced conductive fiber development is expected to significantly promote LM applications in wearable electronics and smart textile systems.
Wearable Electronic Devices ; Polyurethanes/chemistry* ; Electric Conductivity ; Gallium/chemistry* ; Metals/chemistry*

ObjectiveTo clarify the graded quantitative diagnostic characteristics of lung qi deficiency syndrome in chronic obstructive pulmonary disease （COPD） based on latent class analysis combined with a hidden structure model. MethodsClinical data， including the four diagnostic methods of traditional Chinese medicine （TCM）， were collected from 745 COPD patients with lung qi deficiency syndrome. Latent class modeling was performed using R 4.1.2 software， and each patient was classified into one of three severity categories （mild， moderate， or severe） based on probabilistic parameterization， parameter estimation， and model fitting. A database was established for different severity levels of lung qi deficiency syndrome. Based on this， Lantern 5.0 software was used to construct hidden structure models for mild， moderate， and severe lung qi deficiency syndrome， and syndrome differentiation rules were developed through comprehensive clustering. ResultsA latent class model was constructed using 28 symptoms and signs with a frequency greater than 10%. Considering TCM theory and model simplicity， the optimal model was determined when the number of latent classes was three， categorizing lung qi deficiency syndrome into mild （298 cases）， moderate （164 cases）， and severe （283 cases）. Hidden structure models were separately developed for each severity level， and syndrome differentiation rules were established. A comparison of common symptoms in the syndrome differentiation rules for mild and moderate lung qi deficiency syndrome showed no statistically significant differences in diagnostic values and weights （P＞0.05）， leading to their combined analysis and the development of a unified syndrome differentiation rule. Value and weight of quantitative diagnosis of mild-to-moderate lung qi deficiency syndrome were as followed： shortness of breath （diagnostic value 9.3， diagnostic weight 86.92%）， dyspnea on exertion （8.2， 76.64%）， low voice and reluctance to speak （6.7， 62.62%）， poor appetite （4.0， 37.38%）， loose stools （4.0， 37.38%）， weak cough sound （2.9， 27.10%）， wheezing （2.3， 21.50%）， fatigue （1.8， 16.82%）， spontaneous sweating （1.7， 15.89%）， susceptibility to colds （1.6， 14.95%）， swollen tongue （1.4， 13.08%）， teeth marks on the tongue edge （1.2， 11.21%）， deep pulse （1.6， 14.95%）， with a diagnostic threshold of 10.3. Value and weight of quantitative diagnosis of severe lung qi deficiency syndrome were as followed： weak cough sound （15.1， 61.13%）， soreness and weakness of the waist and knees （12.6， 51.01%）， shortness of breath （11.1， 44.94%）， low voice and reluctance to speak （8.3， 33.60%）， frequent nocturia （6.1， 24.70%）， spontaneous sweating （3.7， 14.98%）， susceptibility to colds （3.5， 14.17%）， teeth marks on the tongue edge （7.8， 31.58%）， pale tongue body （1.9， 7.69%）， white tongue coating （5.5， 22.27%）， thin pulse （1.5， 6.07%）， with a diagnostic threshold of 23.7. ConclusionThe combination of latent class analysis and a hideen structure model effectively clarified the graded quantitative diagnostic characteristics of lung qi deficiency syndrome， providing a reference for the quantitative diagnosis of other fundamental syndromes in TCM.

ObjectiveTo analyze the differences in color， odor and volatile components of Citri Reticulatae Pericarpium（CRP） before and after being stir-fried with Halloysitum Rubrum， and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the volatile components were analyzed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. According to the principle of variable importance in the projection（VIP） value>1.5， volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose， the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum， of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected， including α-pinene， β-myrcene， linalool， sabinene， ocimene isomer mixture， A-ocimene， and δ-elemene. After being processed with Halloysitum Rubrum， the brightness value（L^*）， yellow-blue value（b^*） and total chromatic value（E^*_ab） of CRP were decreased（P<0.01）， and red-green value（a^*） was increased（P<0.01）， the response values of S4， S5， S10 and S13 sensors were significantly increased（P<0.05）， and the response values of S3 and S8 sensors were significantly decreased（P<0.05）. Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L^* and E^*_ab， but positively correlated with a^*. Sabinene was positively correlated with L^* and E^*_ab. Linalool was positively correlated with L^* and E^*_ab， and negatively correlated with a^*. The ocimene isomer mixture was positively correlated with the L^*. ConclusionAfter being processed with Halloysitum Rubrum， the appearance color， odor and volatile components of CRP change significantly， and α-pinene， β-myrcene， sabinene， linalool and A-ocimene are the characteristic volatile components before and after processing， which can provide references for the quality evaluation and clinical application of CRP and its processed products.