OBJECTIVE To ensure the safety of patients’ drug use and control the risk of medical insurance expenditure by upgrading the pre-prescription review system to conduct pre-review on prescriptions from internet hospitals and external prescriptions， as well as to review the payment methods of drugs （including in-hospital and external drug dispensing）. METHODS The data interfaces of prescriptions from internet hospitals and external prescriptions were integrated to achieve real-time rational drug use intervention. Additionally， an intelligent review project for payment method was added to precisely intervene in the medical insurance payment methods of drugs. The effect of the system upgrade was evaluated by comparing the qualification rates of prescriptions from internet hospitals and external prescriptions and the suspected amounts of drug violations from January to April 2025 （before the system upgrade） and May to August 2025 （after the system upgrade）. RESULTS After the upgrade of the pre-prescription review system， the qualification rates of prescriptions from internet hospitals and external prescriptions increased by 3.5% [95% confidence interval （CI）＝0.3%-6.7%， P ＝0.037 ] ； the suspected amounts of drug violations decreased to 52.9% of the pre-upgrade level （95%CI＝31.6%-88.5%， P ＝0.026）， and the average monthly sequential decrease was 29.5% （95%CI＝12.2%-43.4%， P ＝0.012）. Moreover， the addition of the intelligent review project for payment methods promoted the management of off-label drug use in our hospital. After the upgrade， a total of 79 filling valid applications for off-label drug use were received and archived. CONCLUSIONS The upgrade of the pre-prescription review system effectively improves the review qualification rates of prescriptions from internet hospitals and external prescriptions and the accuracy of medical insurance payment for drugs， and strengthens the supervision of off-label drug use， achieving dual guarantees of clinical rationality and medical insurance compliance.

AIM:To investigate the effect of ranibizumab on blood flow density in different regions of the macula in patients with macular edema(ME)secondary to ischemic and non-ischemic branch retinal vein occlusion(BRVO).METHODS:This retrospective study enrolled patients with BRVO-ME who were treated at the hospital from September 2019 to March 2021. Patients were divided into ischemic and non-ischemic groups based on fundus findings. All patients received intravitreal injections of ranibizumab once monthly for three consecutive months. Best corrected visual acuity(BCVA), central macular thickness(CMT), and macular blood flow density were measured before treatment and at 1 d, 1 wk, 1 and 3 mo after treatment.RESULTS: A total of 46 patients(46 eyes)with BRVO-ME were included, comprising 21 eyes in the ischemic group(7 males, 14 females; mean age 55.81±10.36 y)and 25 eyes in the non-ischemic group(11 males, 14 females; mean age 54.84±9.81 y). At 3 mo after treatment, BCVA(LogMAR)in the non-ischemic group was superior to that in the ischemic group(0.19±0.19 vs 0.38±0.27, P=0.009). Analysis of CMT changes showed that the reduction amplitude in the ischemic group was significantly greater than that in the non-ischemic group at both 1 and 3 mo after treatment(all P<0.05). Blood flow densities in the whole, parafoveal, and perifoveal regions of the superficial capillary plexus(SCP), as well as in the whole and perifoveal regions of the deep capillary plexus(DCP), were significantly lower in ischemic patients than in non-ischemic patients, while blood flow density in the foveal region of DCP was significantly higher in the ischemic group(all P<0.05).CONCLUSION: Ranibizumab is effective for both types of patients. Non-ischemic patients have a better long-term visual prognosis, and the advantage may be related to better blood flow perfusion patterns in specific areas 3 mo after treatment. Monitoring changes in blood flow density in these areas can help provide personalized treatment for patients.

ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD. Methods: This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared. Results: Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn’s disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001). Conclusions Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD.

Parkinson’s disease (PD) is a common neurodegenerative disorder that significantly impacts patients’ independence and quality of life, imposing a substantial burden on both individuals and society. Although dopaminergic replacement therapies provide temporary relief from various symptoms, their long-term use often leads to motor complications, limiting overall effectiveness. In recent years, non-invasive deep brain stimulation (DBS) techniques have emerged as promising therapeutic alternatives for PD, offering a means to modulate deep brain regions with high precision without invasive procedures. These techniques include temporal interference stimulation (TIs), low-intensity transcranial focused ultrasound stimulation (LITFUS), transcranial magneto-acoustic stimulation (TMAS), non-invasive optogenetic modulation, and non-invasive magnetoelectric stimulation. They have demonstrated significant potential in alleviating various PD symptoms by modulating neural activity within specific deep brain structures affected by the disease. Among these approaches, TIs and LITFUS have received considerable attention. TIs generate low-frequency interference by applying two slightly different high-frequency electric fields, targeting specific brain areas to alleviate symptoms such as tremors and bradykinesia. LITFUS, on the other hand, uses low-intensity focused ultrasound to non-invasively stimulate deep brain structures, showing promise in improving both motor function and cognition in PD patients. The other three techniques, while still in early research stages, also hold significant promise for deep brain modulation and broader clinical applications, potentially complementing existing treatment strategies. Despite these promising findings, significant challenges remain in translating these techniques into clinical practice. The heterogeneous nature of PD, characterized by variable disease progression and individualized treatment responses, necessitates flexible protocols tailored to each patient’s unique needs. Additionally, a comprehensive understanding of the mechanisms underlying these treatments is crucial for refining protocols and maximizing their therapeutic potential. Personalized medicine approaches, such as the integration of neuroimaging and biomarkers, will be pivotal in customizing stimulation parameters to optimize efficacy. Furthermore, while early-stage clinical trials have reported improvements in certain symptoms, long-term efficacy and safety data are limited. To validate these techniques, large-scale, multi-center, randomized controlled trials are essential. Parallel advancements in device design, including the development of portable and cost-effective systems, will improve patient access and adherence to treatment protocols. Combining non-invasive DBS with other interventions, such as pharmacological treatments and physical therapy, could also provide a more comprehensive and synergistic approach to managing PD. In conclusion, non-invasive deep brain stimulation techniques represent a promising frontier in the treatment of Parkinson’s disease. While they have demonstrated considerable potential in improving symptoms and restoring neural function, further research is needed to refine protocols, validate long-term outcomes, and optimize clinical applications. With ongoing technological and scientific advancements, these methods could offer PD patients safer, more effective, and personalized treatment options, ultimately improving their quality of life and reducing the societal burden of the disease.