ObjectiveProtein-protein interactions (PPIs) are fundamental to the execution of biological functions within living cells. However, traditional biochemical methods, such as co-immunoprecipitation (Co-IP), often fail to capture transient, weak, or membrane-associated interactions due to the stringent detergent requirements for cell lysis. Proximity labeling (PL) has emerged in recent years as a transformative technology for mapping the proteomes of specific subcellular compartments and identifying dynamic interactomes in situ. Golgi protein 73 (GP73, also known as GOLPH2), a resident type II Golgi transmembrane protein, is a well-recognized clinical biomarker for liver diseases, including hepatocellular carcinoma (HCC). Despite its clinical significance, the comprehensive physiological and pathological functions of GP73 remain partially understood. This study aims to establish an APEX2-mediated proximity labeling system specifically targeting GP73 to map its interactome in a living cellular environment, thereby providing new insights into its molecular roles and regulatory mechanisms. MethodsTo achieve spatial specificity, we first constructed a stable cell line expressing a fusion protein consisting of GP73 and the engineered soybean peroxidase APEX2. The localization of the GP73-APEX2 fusion protein was validated to ensure it correctly targeted the Golgi apparatus. The proximity labeling reaction was initiated by incubating the cells with biotin-phenol (BP) for 30 min, followed by a brief (1 min) treatment with1 mmol/L hydrogen peroxide (H₂O₂). This catalytic reaction converts BP into highly reactive, short-lived biotin-phenoxyl radicals that covalently attach to endogenous proteins within a small labeling radius of the GP73-APEX2 enzyme. Subsequently, the cells were quenched, and biotinylated proteins were enriched using high-affinity streptavidin-coated magnetic beads. The captured “neighbor” proteins were subjected to on-bead digestion and analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) for high-throughput identification. Rigorous bioinformatics analysis, including Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction network mapping, was performed to interpret the biological significance of the identified candidates. ResultsOur results demonstrate the successful establishment of a robust and sensitive APEX2-based proximity labeling system for GP73. We identified a total of 95 high-confidence interacting proteins that were significantly enriched in the GP73 proximity proteome compared to control groups. Bioinformatics analysis revealed that these interactors were predominantly associated with biological processes such as vesicular transport, protein localization, and, most notably, molecular functions related to “ribosome binding” and “translation regulation”. This suggested an unexpected role for the Golgi-resident GP73 in the cellular translation machinery. To validate these findings, we performed targeted biochemical assays which confirmed a direct interaction between GP73 and the subunits of the eukaryotic translation initiation factor 3 (eIF3) complex, specifically EIF3G and EIF3I. Furthermore, functional validation using the surface sensing of translation (SUnSET) assay—a non-radioactive method to monitor protein synthesis—revealed that the overexpression of GP73 significantly promoted global protein translation levels in the cell, whereas its depletion or inhibition resulted in reduced translation efficiency. ConclusionThis study successfully utilized APEX2-mediated proximity labeling to provide the first systematic map of GP73 interactome in living cells. Our findings uncover a novel, unconventional function of GP73 as a regulator of cellular protein translation, likely mediated through its interaction with the eIF3 complex. This discovery significantly broadens our understanding of the biological roles of GP73 beyond its traditional function in the Golgi apparatus and suggests that it may act as a bridge between Golgi-related trafficking and the protein synthesis machinery. Furthermore, the technical framework established in this study provides a valuable template for investigating other complex organelle-associated protein networks and resolving transient macromolecular interactions in various physiological and pathological contexts.

Background: Recurrent pregnancy loss undermines the physical and mental health of women. Recent randomized controlled trials have reported some effects of traditional Chinese medicine (TCM); however, whether various TCM methods have different effectiveness remains unclear. Objective: To comprehensively evaluate the efficacy and adverse events of TCM for patients with RPL and to explore whether various TCM methods have different effectiveness. Methods: Ten databases were searched up to May 27, 2024. The risk of bias was assessed using the RoB2 tool. The certainty of the evidence was evaluated using the grading of Recommendations, Assessment, Development, and Evaluation tool. Pairwise and network analyses were conducted using Stata 18.0. Results: A total of 47 randomized controlled trials enrolling 6678 women with RPL were included. Pairwise analysis showed that use of TCM had a significantly lower miscarriage rate (RR 0.50 [95% CI 0.45, 0.55]), lower preterm birth rate (RR 0.81 [95% CI 0.67, 0.98), and lower adverse event rate (RR 0.46 [95% CI 0.37, 0.58]). Moreover, use of TCM was associated with a higher alive-fetus rate (RR 1.21 [95% CI 1.15, 1.26]), live-birth rate (RR 1.20 [95% CI 1.15, 1.25]), and full-term rate (RR 1.37 [95% CI 1.23, 1.53]) compared with nonuse of TCM. Network analysis demonstrated that Bushenshugan combined with conventional Western medicine was ranked the best for the reduction of miscarriage rate. Discussion: Use of TCM is more likely to improve pregnancy outcomes and reduce adverse events compared with nonuse of TCM in patients with RPL. Different TCM methods have differences in reducing the miscarriage rate. The Bushenshugan method might be a potential optimal TCM therapy, but more high-quality evidence is needed to further validate and evaluate the efficacy and safety.

Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

Plant-derived extracellular vesicles (PDEVs) are nanoscale extracellular vesicles secreted by plant cells, characterized by a lipid bilayer structure. These vesicles carry a variety of bioactive molecules, including proteins, nucleic acids, and lipids, and play essential roles in intercellular communication and physiological regulation in plants. Compared to animal-derived extracellular vesicles, PDEVs offer several advantages, such as a broad range of sources, high biocompatibility, low immunogenicity, and low production costs. Furthermore, PDEVs have demonstrated remarkable potential as natural nanocarriers for drug delivery, due to their ability to efficiently traverse biological barriers, such as the blood-brain barrier, making them promising candidates for drug delivery systems. This review systematically elaborates on the complex composition of PDEVs, which consists of lipids, proteins, and nucleic acids, the typical structural characteristics of their lipid bilayers ranging from 30 to 150 nm, and their versatile loading capabilities as drug carriers, efficiently encapsulating various types of therapeutic agents such as hydrophilic small molecules, hydrophobic drugs, nucleic acids, and proteins. We systematically summarize the recent advancements in strategies for enhancing the loading efficiency of PDEVs, which include methods such as co-incubation, ultrasound-assisted loading, electroporation, freeze-thaw cycles, and microfluidic technology. These techniques are evaluated based on their underlying principles, suitable drug types, and their respective advantages. In addition to loading strategies, we focus on the engineered approaches to achieve targeted delivery using PDEVs, such as genetic engineering modifications, chemical ligand conjugation, membrane fusion technology, and polyethylene glycol (PEG) modification. We discuss the mechanisms of these strategies in enhancing targeting efficiency, prolonging in vivo circulation time, and improving therapeutic efficacy. Further, this review highlights the application of PDEVs in various disease models, including tumor, skin inflammation, metabolic disorders, and neurodegenerative diseases, showcasing their therapeutic potential as multifunctional delivery platforms. The ability of PDEVs to encapsulate diverse therapeutic agents and target specific tissues or cells opens up new avenues for the treatment of complex diseases, offering advantages over conventional drug delivery systems. However, despite the promising applications of PDEVs, several challenges remain in their development and clinical translation. These challenges include variability in source materials, standardization of preparation processes, quality control, scalability of production, and the need for clinical validation. To overcome these obstacles, the integration of advanced technologies such as artificial intelligence-assisted design and multi-omics analysis is proposed as a way to facilitate the precise development of PDEVs. These emerging technologies hold the potential to further enhance the precision and effectiveness of plant-based drug delivery systems, ultimately advancing the field of precision medicine. In conclusion, the use of PDEVs as a platform for drug delivery represents a promising area of research with the potential to revolutionize therapeutic strategies. Their ability to encapsulate and deliver a wide variety of bioactive molecules, along with their inherent advantages in biocompatibility and versatility, makes them a valuable tool in the development of more efficient and targeted therapeutic interventions. Continued research and innovation in this field will pave the way for the clinical implementation of PDEVs in the treatment of various diseases, offering new hope for more effective and sustainable therapeutic options.

Objective This study aimed to investigate the genetic diversity, differentiation, and population structure of Aedes albopictus across different geographical regions in Shandong Province, and to explore the relationship between genetic diversity and geographical distribution. Methods Between July and August 2024, ten Ae. albopictus populations were sampled from seven cities in Shandong Province. Genomic DNA was extracted from individual mosquitoes, and the mitochondrial cytochrome c oxidase subunit I(COⅠ)gene was amplified using PCR and sequenced. The obtained sequences were verified using BLAST and analyzed with MAFFT, MEGA 11, DnaSP v6.12, Arlequin 3.5, PopART 1.7, STRUCTURE 2.3.4 and the R packages adegenet and vegan to assess genetic diversity and population structure. Results A total of 229 COⅠ sequences(662 bp) was obtained, revealing ten variable sites with no insertions or deletions. The overall base composition showed an AT bias of 67.7%. Haplotype analysis identified 11 haplotypes, with Hap2 being the dominant and most widely distributed haplotype across all populations. Neutrality tests showed significant population expansion only in the Rizhao population. Mantel testing result revealed that geographical distance does not significantly impede gene flow. Overall, genetic differentiation among populations was low, indicating frequent gene flow. When combined with additional samples from Shanghai, Fujian, Guangdong, Yunnan, Hainan and Guangxi, STRUCTURE, UPGMA and DAPC analyses revealed two primary genetic clusters of Ae. albopictus. Conclusions Ae. albopictus populations in Shandong Province exhibit frequent gene flow, low genetic differentiation, and relatively low overall genetic diversity. However, the Rizhao population showed signs of recent expansion, highlighting the need for enhanced surveillance and targeted control measures in this area.

ObjectiveTo summarize the research results on the toxic mechanism and the relevant regulatory policies at home and abroad of pyrrolizidine alkaloids （PAs）， the main toxic components， in Senecionis Scandentis Herba， thereby providing insights into the clinical use and scientific regulation of Senecionis Scandentis Herba. MethodsMultiple Chinese and English databases including PubMed， ScienceDirect， Elsevier， China national knowledge infrastructure （CNKI）， Wanfang Data， and VIP were searched， with "Senecio，" "PSenecio scandens，" and "pyrrolizidine alkaloids" as search terms. The relevant articles published from 1959 to 2025 were retrieved and analyzed， and 79 articles were finally selected for review. ResultsThe chemical components of Senecionis Scandentis Herba include alkaloids， flavonoids， volatile oils， sesquiterpenes， jacaranone derivatives， and organic acids， among which alkaloids are the most toxic components， followed by jacaranone derivatives. PAs are metabolized into highly active pyrrole derivatives in the liver， which can cause serious adverse reactions such as sinusoidal obstruction syndrome and DNA damage. The content of PAs varies significantly due to the origin， harvest period， and medicinal parts. There have been reports of clinical liver injury caused by preparations containing Senecionis Scandentis Herba， and some preparations have a daily intake of PAs exceeding the international safety threshold. Currently， international organizations have set limited standards for PAs， while China only controls the content of adonifoline， and the supervision is not yet perfect. ConclusionAlthough Senecionis Scandentis Herba has medicinal value， its PAs have significant toxicological properties. This is a problem that cannot be ignored and needs to be overcome in the use of Senecionis Scandentis Herba. Therefore， it is necessary to strengthen the quality control of raw materials， establish a more comprehensive limited standard for PAs， and optimize the medication strategy in combination with traditional Chinese medicine theory to ensure the safety of clinical medication.

ObjectiveTo summarize the research results on the toxic mechanism and the relevant regulatory policies at home and abroad of pyrrolizidine alkaloids （PAs）， the main toxic components， in Senecionis Scandentis Herba， thereby providing insights into the clinical use and scientific regulation of Senecionis Scandentis Herba. MethodsMultiple Chinese and English databases including PubMed， ScienceDirect， Elsevier， China national knowledge infrastructure （CNKI）， Wanfang Data， and VIP were searched， with "Senecio，" "PSenecio scandens，" and "pyrrolizidine alkaloids" as search terms. The relevant articles published from 1959 to 2025 were retrieved and analyzed， and 79 articles were finally selected for review. ResultsThe chemical components of Senecionis Scandentis Herba include alkaloids， flavonoids， volatile oils， sesquiterpenes， jacaranone derivatives， and organic acids， among which alkaloids are the most toxic components， followed by jacaranone derivatives. PAs are metabolized into highly active pyrrole derivatives in the liver， which can cause serious adverse reactions such as sinusoidal obstruction syndrome and DNA damage. The content of PAs varies significantly due to the origin， harvest period， and medicinal parts. There have been reports of clinical liver injury caused by preparations containing Senecionis Scandentis Herba， and some preparations have a daily intake of PAs exceeding the international safety threshold. Currently， international organizations have set limited standards for PAs， while China only controls the content of adonifoline， and the supervision is not yet perfect. ConclusionAlthough Senecionis Scandentis Herba has medicinal value， its PAs have significant toxicological properties. This is a problem that cannot be ignored and needs to be overcome in the use of Senecionis Scandentis Herba. Therefore， it is necessary to strengthen the quality control of raw materials， establish a more comprehensive limited standard for PAs， and optimize the medication strategy in combination with traditional Chinese medicine theory to ensure the safety of clinical medication.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes in chronic persistent immunoglobulin A nephropathy(IgAN)and to explore the relationship between TCM syndromes and prognosis based on real-world research.Methods From January 2018 to January 2024,a total of 80 patients with chronic persistent IgAN who were admitted to Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University were included.The clinical baseline data and prognosis-related information were collected.The main outcome indicators were defined as renal failure events of glomerular filtration rate(eGFR)decreased by＞50%,serum creatinine doubled or end-stage renal disease(ESRD).The distribution of TCM syndromes in chronic persistent IgAN and the relationship between different deficiency syndromes and prognosis were preliminarily discussed.Results(1)Among the 80 patients with chronic persistent IgAN,the syndrome manifestations with an occurrence frequency of more than 30%in descending order were foamy urine(75.00%),fatigue and lassitude(71.25%),waist ache(61.25%),dry mouth(31.25%),lower extremity edema(31.25%),aversion to cold and cold limbs(30.00%),and insomnia(30.00%).(2)The commonly-seen root-deficiency syndrome in patients with chronic persistent IgAN was qi and yin deficiency syndrome,with a total of 28 cases(35.00%).And other root-deficiency syndromes were spleen and kidney yang deficiency syndrome in 22 cases(27.50%),lung and spleen qi deficiency syndrome in 15 cases(18.75%),and liver and kidney yin deficiency syndrome in 15 cases(18.75%).The commonly-seen complicated syndrome was water-damp syndrome,with a total of 17 cases(21.25%).The other complicated syndromes were damp-heat syndrome in 15 cases(18.75%),blood-stasis syndrome in 9 cases(11.25%),phlegm-damp syndrome in 7 cases(8.75%),turbidity-toxin syndrome in 5 cases(6.25%),liver depression syndrome in 3 cases(3.75%),and cold-damp syndrome in 1 case(1.25%).(3)Among the 80 patients with chronic persistent IgAN,21 cases(26.25%)had renal failure events,and their syndrome types were lung and spleen qi deficiency syndrome in 9 cases(60.00%),qi and yin deficiency syndrome in 3 cases(10.71%),liver and kidney yin deficiency syndrome in 3 cases(20.00%),and spleen and kidney yang deficiency syndrome in 6 cases(27.27%).The incidence of renal failure events in patients with lung and spleen qi deficiency syndrome was significantly higher than that in the other three syndrome types,and the chi-square test showed that the difference was statistically significant(P＜0.05).(4)Kaplan-Meier survival analysis showed that the cumulative incidence of 2-year and 5-year endpoint events in patients with lung and spleen qi deficiency syndrome was 23.10%and 46.20%,respectively,and the final incidence was 85.00%.The cumulative incidence of 2-year and 5-year endpoint events in patients with other deficiency syndromes was 4.50%and 19.70%,respectively,and the final incidence was 71.60%.The intergroup comparison(tested by Log-rank)showed that the incidence of renal failure events in patients with lung and spleen qi deficiency syndrome was significantly higher than that in patients with other root-deficiency syndromes,and the difference was statistically significant(P＜0.05).(5)COX proportional hazard regression analysis showed that lung and spleen qi deficiency syndrome(HR=7.755,95%CI 1.631-36.874,P＜0.05)and anemia(HR=8.205,95%CI 1.007-66.857,P＜0.05)were the independent risk factors for renal failure events in patients with chronic persistent IgAN.Conclusion Qi and yin deficiency syndrome is the most common syndrome in the patients with chronic persistent IgAN,and lung and spleen qi deficiency syndrome and anemia are the independent risk factors for renal failure events in IgAN.

Objective To explore the validity and feasibility of the left transthoracic and esophageal hiatal approach for Siewert type Ⅱ adenocarcinoma of the esophagogastric junction under a single position.Methods The clinical data of 64 patients with Siewert type Ⅱ AEG(single position transthoracic approach group)treated with the left transthoracic and esophageal hiatal approach under a single position and 56 patients with the laparoscopic transesophageal slit approach(transabdominal approach group)in the Department of Thoracic Surgery,Huaihe Hospital of Henan University,from January 2017 to December 2018 were retrospectively analyzed.The clinical and pathological data,perioperative indicators(operation time,intraoperative blood loss,postoperative first ambulation time,postoperative first peristalsis time,postoperative drainage volume at 3 d,incidence of postoperative complications,postoperative hospital stay),postoperative complications(positive surgical margin,proximal esophageal resection margin,tumor diameter,total number of dissected lymph nodes,positive lymph node dissection rate,postoperative histopathology,and TNM staging of tumor pathology),and survival indicators(tumor recurrence and metastasis rate and survival at 1 month,3 months,6 months,1 year,3 years,5 years after surgery)were compared between the two groups.Kaplan-Meier method was used to analyze the postoperative survival rate of the two groups.Univariate analysis using χ2 test was employed to analyze factors influencing 5-year postoperative survival rate in Siewert type Ⅱ AEG patients.Results No significant difference was observed in clinical and pathological data,such as gender,age,American Society of Anesthesiologists(ASA)grade,tumor differentiation,pTNM stage,and tumor diameter between the two groups(P>0.05).No significant differences were noted in intraoperative blood loss,incidence of postoperative complications,and survival rates at 1 month,3 months,6 months,1 year,and 3 years after surgery between the two groups(P>0.05).The single position transthoracic approach group exhibited a higher postoperative drainage volume at 3 d compared to the transabdominal approach group(P<0.001),a shorter surgical time(P<0.001),a longer time to first mobilization,first intestinal peristalsis,and hospital stay after surgery(P<0.01),a longer proximal esophageal margin(P<0.001),a higher total number of lymph node dissections(P<0.001),and a higher positive lymph node dissection rate(P<0.05)than the transabdominal approach group.The 5-year recurrence-free survival rate of the single position transthoracic approach group was higher than that of the transabdominal approach group,with a statistically significant difference(P=0.013).The Kaplan-Meier survival curve showed no statistically significant difference in the 5-year overall survival rate between the two groups of patients after surgery(P=0.456).The results of univariate analysis indicated that there are significant relationships between tumor differentiation degree,pTNM stage,tumor diameter,and lymph node positivity rate with the 5-year postoperative survival rate in Siewert type Ⅱ AEG patients(P<0.05).Conclusion Siewert type Ⅱ AEG patients can be treated with the left transthoracic and esophageal hiatal approach under a single position,achieving the same effect as laparoscopic transesophageal slit approach,and it can be actively promoted as a complementary choice of operation in the clinic.

Objective To investigate the density,species composition,and seasonal prevalence of domestic rodents in different habitats within Lanzhou garrisons,providing basic information for rodent prevention and control.Methods A total of 12 monitoring sites were sampled across urban,suburban,and rural residential areas from 2014 to 2022.Rodent density was monitored using the night-trapping method in the middle of odd-numbered months.Results From 2014 to 2022,346 domestic rodents were captured using 122 035 effective traps,with an average domestic rodent density of 0.28％.The highest domestic rodent density was 0.63％in 2016,and the lowest was 0.07％in 2020,showing significant differences across years,with an overall trend of initially decreasing and then increasing(χ2=136.555,P<0.001).The dominant species was Rattus norvegicus,accounting for 83.24％of the total rodents captured.Rattus norvegicus accounted for a relatively high proportion across different years,with a statistically significant difference in species composition(χ2=20.931,P<0.05).Rodent densities and species composition also varied significantly among the monitored habitats(P<0.001),with the highest densities observed in rural residential areas and the lowest in urban areas.Seasonal variation in rodent densities showed a bimodal pattern,with smaller peaks in January or March and a larger peak in July.Conclusions Domestic rodent density in Lanzhou garrisons has shown an upward trend in the past few years.Rodent control measures should focus on barracks in rural residential areas,with targeted interventions to reduce the risk of rodent-borne diseases.