BackgroundGenetic factor plays an important role in the pathogenesis of panic disorder. Previous studies have revealed that immune system dysregulation is closely related to mental disorders such as panic disorder， while the relationship between panic disorder and immune-related gene expression remains unclear. ObjectiveTo explore the relationship between the expression of CXCL8， IL6R， JUN， PTGS2， TGFBR1， TLR2， CCR4 genes and panic disorder， providing references for the diagnosis and treatment of panic disorder. MethodsA total of 52 patients who met the diagnostic criteria for panic disorder according to the Diagnosed and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were enrolled at the Psychosomatic Medicine Center of Sichuan Provincial People's Hospital from January 2020 to March 2021. Another 72 healthy individuals matched for age and gender from Chengdu were concurrently recruited as control group. The Panic Disorder Severity Scale （PDSS） was used to assess the severity of symptoms in panic disorder patients. Quantitative real-time polymerase chain reaction （PCR） was used to detect gene expression levels in two groups. Spearman correlation analysis was adopted to determine the correlation between PDSS score and immune-related gene expression in research group. ResultsThe expression of the JUN， PTGS2 and TGFBR1 genes were significant higher in panic disorder patients than those in control group （Z=-4.172， -2.086， -3.018， P<0.05 or 0.01）. After false discovery rate （FDR） correction for multiple testing， the differential expression of JUN and TGFBR1 genes remained statistically significant between two groups （P<0.05）. There was no significant difference in the expression of CCR4， CXCL8， IL6R and TLR2 genes between two groups （P>0.05）. Correlation analysis revealed that the expression of the JUN gene in panic disorder patients was positively correlated with PDSS score （r=0.360， P<0.01）， while the CCR4， CXCL8， IL6R， PTGS2， TGFBR1 and TLR2 genes showed no statistically significant correlation with the PDSS score （P>0.05）. ConclusionThe expression of the JUN and TGFBR1 genes may be associated with panic disorder， and the expression of the JUN gene correlated with the severity of panic disorder. ［Funded by Science and Technology Plan Project of Sichuan Provincial Department of Science and Technology （number， 2021YJ0440）］

ObjectiveTo collate and compare the characteristics and differences in the methods for constructing animal models of different subtypes of gastroesophageal reflux disease （GERD） based on literature， providing a reference for researchers in this field regarding animal model construction. MethodsExperimental studies related to GERD including reflux esophagitis （RE）， nonerosive reflux disease （NERD） and Barrett's esophagus （BE） model construction from January 1， 2014 to January 27， 2024， were retrieved from databases such as CNKI， Wanfang， VIP， Web of Science， and Pubmed. Information on animal strains， genders， modeling methods including disease-syndrome combination models， modeling cycles were extracted； for studies with model evaluation， the methods of model evaluation were also extracted； then analyzing all those information. ResultsA total of 182 articles were included. SD rats were most frequently selected when inducing animal models of RE （88/148， 59.46%） and NERD （9/14， 64.29%）. For BE， C57BL/6 mice were most commonly used （11/20， 55.00%）. Male animals （RE： 111/135， 82.22%； NERD： 11/14， 78.57%； BE： 10/12， 83.33%） were the most common gender among the three subtypes. The key to constructing RE animal models lies in structural damage to the esophageal mucosal layer， gastric content reflux， or mixed reflux， among which forestomach ligation + incomplete pylorus ligation （42/158， 26.58%） was the most common modeling method； the key to constructing NERD animal models lies in micro-inflammation of the esophageal mucosa， visceral hypersensitivity， and emotional problems， and intraperitoneal injection of a mixed suspension of ovalbumin and aluminum hydroxide combined with acid perfusion in the lower esophagus （8/14， 57.14%） was the most common modeling method； the key to constructing BE animal models lies in long-term inflammatory stimulation of the esophageal mucosa and bile acid reflux， and constructing interleukin 2-interleukin 1β transgenic mice （7/25， 28.00%） was the most common modeling method. Adverse psychological stress was the most common method for inducing liver depression. ConclusionsThe construction key principles and methodologies for RE， NERD， and BE animal models exhibit significant differences. Researchers should select appropriate models based on subtype characteristics （e.g.， RE focusing on structural damage， NERD emphasizing visceral hypersensitivity）. Current studies show insufficient exploration of traditional Chinese medicine disease-syndrome combination models. Future research needs to optimize syndrome modeling approaches （e.g.， composite etiology simulation） and establish integrated Chinese-Western medicine evaluation systems to better support mechanistic investigations of traditional Chinese medicine.

The circadian clock is a highly conserved timekeeping system in organisms, which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression. Substantial clinical and experimental evidence has established a close association between circadian rhythm disruption and the development of various malignancies. Research has revealed characteristic alterations in the circadian gene expression profiles in tumor tissues, primarily manifested as a dysfunction of core clock components (particularly circadian locomotor output cycles kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1)) and the widespread dysregulation of their downstream target genes. Notably, CLOCK demonstrates non-canonical oncogenic functions, including epigenetic regulation via histone acetyltransferase activity and the circadian-independent modulation of cancer pathways. This review systematically elaborates on the oncogenic mechanisms mediated by CLOCK/BMAL1, encompassing multidimensional effects such as cell cycle control, DNA damage response, metabolic reprogramming, and tumor microenvironment (TME) remodeling. Regarding the therapeutic strategies, we focus on cutting-edge approaches such as chrononutritional interventions, chronopharmacological modulation, and treatment regimen optimization, along with a discussion of future perspectives. The research breakthroughs highlighted in this work not only deepen our understanding of the crucial role of circadian regulation in cancer biology but also provide novel insights for the development of chronotherapeutic oncology, particularly through targeting the non-canonical functions of circadian proteins to develop innovative anti-cancer strategies.
Humans ; ARNTL Transcription Factors/physiology* ; Neoplasms/therapy* ; CLOCK Proteins/physiology* ; Circadian Clocks/genetics* ; Animals ; Circadian Rhythm/genetics* ; Tumor Microenvironment ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic

Nanocarrier-based drug delivery systems (nDDSs) present significant opportunities for improving disease treatment, offering advantages in drug encapsulation, solubilization, stability enhancement, and optimized pharmacokinetics and biodistribution. nDDSs, comprising lipid, polymeric, protein, and inorganic nanovehicles, can be guided by or respond to biological cues for precise disease treatment and management. Equipping nanocarriers with tissue/cell-targeted ligands enables effective navigation in complex environments, while functionalization with stimuli-responsive moieties facilitates site-specific controlled release. These strategies enhance drug delivery efficiency, augment therapeutic efficacy, and reduce side effects. This article reviews recent strategies and ongoing advancements in nDDSs for targeted drug delivery and controlled release, examining lesion-targeted nanomedicines through surface modification with small molecules, peptides, antibodies, carbohydrates, or cell membranes, and controlled-release nanocarriers responding to endogenous signals such as pH, redox conditions, enzymes, or external triggers like light, temperature, and magnetism. The article also discusses perspectives on future developments.
Humans ; Drug Carriers/chemistry* ; Drug Delivery Systems/methods* ; Delayed-Action Preparations/chemistry* ; Nanoparticles/chemistry* ; Animals ; Drug Liberation ; Nanomedicine

Objective:To investigate the consistency and sensitivity of minimal residual disease (MRD) detected by multicolor flow cytometry (FCM) and real-time quantitative polymerase chain reaction (RQ-PCR) in patients with acute myeloid leukemia (AML) accompanied by monocytic differentiation after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective case series study was conducted. A total of 218 patients diagnosed with AML accompanied by monocytic differentiation who underwent allo-HSCT in Peking University People's Hospital between January 2017 and December 2021 were included. MRD was detected by using bone marrow FCM and RQ-PCR at predefined intervals (at 1-, 2-, 3-, 4.5-, 6-, 9-, and 12-month before and after transplantation). Patients were grouped based on AML-related specific genes, and dynamic changes in MRD results detected by FCM and RQ-PCR after transplantation were analyzed to evaluate the correlation with post-transplant relapse.Results:A total of 218 enrolled patients included 114 males and 106 females, with the median age of 32 years (1-65 years). The median follow-up duration was 218 d (21-1 541 d). Hematologic relapse occurred in 26 patients (12.7%), with a median relapse time of 272 d (83-934 d); 35 patients (15.9%) died, including 15 (6.9%) due to leukemia relapse and 20 (9.2%) due to transplant-related mortality. Predictive markers for relapse included once WT1 positive (WT1+once), twice WT1 positive (WT1+twice), CBFβ::MYH11 fusion genes positive, mixed-lineage leukemia (MLL)-related fusion genes positive, AML1::ETO fusion genes positive, and once FCM positive (FCM+once), twice FCM positive (FCM+twice). The overall consistency rate between FCM and RQ-PCR for MRD detection in AML patients accompanied by monocytic differentiation after transplantation was 75.7% (165/218). The consistency rate of MRD detection results in WT1+once, WT1+ twice, MLL-related fusion gene positive, and NPM1 gene mutation positive with FCM was higher than the average value (>75.7%), while the consistency rate of MRD detection results in AML1::ETO and CBFβ::MYH11 fusion gene positive with FCM was lower than the average value (<75.7%). Notably, persistent low-level positivity without relapse after transplantation occurred in cases with WT1 (15 patients), NPM1 (2 patients), CBFβ::MYH11 (11 patients), or AML1::ETO (2 patients); in contrast, MLL-related fusion genes (particularly MLL::AF6 and MLL::AF9) positive after transplantation indicated relapse in patients. The sensitivity and specificity of RQ-PCR for MRD monitoring varied by genetic markers: WT1+once and WT1+twice (sensitivity: 66.7%, 50.0%; specificity: 84.5%, 91.1%, respectively), AML1::ETO (sensitivity: 100.0%; specificity: 50.0%), CBFβ::MYH11 (sensitivity: 100.0%; specificity: 58.6%), MLL-related fusion genes (sensitivity: 75.0%; specificity: 96.4%), and NPM1 (sensitivity: 75.0%; specificity: 91.7%).Conclusions:The sensitivity and specificity of AML-related genetic markers for recurrence prediction show differences. Discrepancies between RQ-PCR and FCM in MRD detection are notable in AML with monocytic differentiation after transplantation. FCM exhibits relatively lower sensitivity for MRD monitoring in this subtype, while RQ-PCR based on AML-related genes may compensate for FCM limitations.

The gut microbiota is of great significance for children's health.An increasing number of studies indicate that gut microbiota is one of the potential mediators affecting human neurodevelopment and neuropsychiatric dysbiosis.In early life，there is a significant overlap between the development window of gut microbiota and the nervous system.Premature infants are at high risk of developing gut microbiota dysbiosis and neurodevelopmental disorders.However，the connection between gut microbiota in early human life and neural development remains unclear.This article reviews the relationship between gut microbiota in early life and neurodevelopment in premature infants，with the aim of contributing to identify predictive biomarkers and potential therapeutic targets for healthy neurological development in premature infants.

Neonatal hyperbilirubinemia constitutes one of the common symptoms during the neonatal period. If it is not controlled and effectively treated in time，bilirubin encephalopathy can occur in severe cases，leading to neurological dysfunction and other adverse consequences. Therefore，early detection and effective treatment of hyperbilirubinemia are particularly crucial. In recent years，with the advancement of medical technology，a variety of new detection and treatment methods have been developed and implemented in clinical practice. This article reviews the traditional tests for neonatal hyperbilirubinemia，including percutaneous bilirubinometry and serum bilirubin level testing，evaluates their accuracy and validity，and describes new advances in detection tools. Meanwhile，the application of phototherapy，medication，and other complementary therapies，as well as their efficacy，is also highlighted. This paper aims to enhance the management level of neonatal hyperbilirubinemia，reduce its potential complications，and improve the prognosis of newborns.

Glaucocalyxin A （GLA） is a natural diterpenoid extracted from Isodon amethystoides belonging to Labiatae. Modern pharmacological research has shown that GLA has anti-inflammatory， anti-tumor， anti-fibrotic， osteoporosis-ameliorating， and cardiovascular system-protecting activities and good biosafety. However， the low content in plants， poor solubility， high metabolic rate， and low bioavailability limit the application of GLA. To address these issues， researchers have studied the total synthesis， structural modification， and nanomedicine development of GLA. By reviewing the available studies about GLA in the past five years， we summarize the research progress in the total synthesis， pharmacological activities and mechanisms， and in vivo metabolic transformation， aiming to provide a theoretical basis for clarifying the specific mechanisms underlying the pharmacological activities of GLA and for further research， development， and clinical applications of GLA.