ObjectiveTo evaluate the efficacy and safety of Janus kinase （JAK） inhibitors combined with Chinese herbal medicine （CHM） in treating rheumatoid arthritis （RA）. MethodsClinical data from 169 RA patients were retrospectively collected. Among them， 71 cases received JAK inhibitors as the control group， while 98 cases received JAK inhibitors plus CHM as the observation group， both treated for 24 weeks. The rheumatoid factor （RF）， cyclic citic peptide antibody （anti-CCP）， erythrocyte sedimentation rate （ESR）， C-reactive protein （CRP）， and white blood cell count （WBC） were recorded before and after treatment. Databases including CNKI， Wanfang， VIP， PubMed and Web of Science were searched from inception till August 31st， 2025 for randomized controlled trials （RCTs） on the combined use of JAK inhibitors and CHM for RA. The methodological quality of the included studies was evaluated using the risk of bias assessment tool. Meta-analyses were performed for RF， anti-CCP， ESR， CRP， 28-joint disease activity score （DAS28）， overall clinical effective rate， and incidence of adverse events. Sensitivity analysis were also performed. ResultsThe retrospective study demonstrated that after treatment， ESR， CRP， and anti-CCP levels decreased in the observation group， while ESR and CRP levels decreased in the control group （P＜0.05）. Moreover， ESR and RF levels in the observation group were lower than those in the control group （P＜0.05）. A total of 9 RCTs involving 770 patients were included in the meta-analysis. The results indicated that the JAK inhibitors plus CHM group was superior to the JAK inhibitors group in reducing RF （MD=-8.97， 95%CI -15.01 to -2.94， P=0.004）， CRP （MD=-3.34， 95%CI -3.82 to -2.86， P＜0.001）， ESR （MD=-5.33， 95%CI -7.98 to -2.69， P＜0.001）， and DAS28 score （MD=-0.54， 95%CI -0.74 to -0.34， P＜0.001）， as well as in improving the overall clinical effective rate （OR=4.53， 95%CI 2.55 to 8.03， P＜0.001）. No statistically significant differences were observed between groups in anti-CCP levels （SMD=-2.08， 95%CI -4.41 to 0.24， P=0.080） or incidence of adverse events （OR=0.93， 95%CI 0.55 to 1.57， P=0.790）. ConclusionThe combination of JAK inhibitors and CHM demonstrates remarkable efficacy in treating RA， contributing to improved disease activity and reduced inflammatory markers with a favorable safety profile.

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.

Objective To evaluate the diagnostic efficacy of different pathogen detection methods in active tuberculosis (ATB) of kidney transplant recipients (KTRs) and analyze their diagnostic value in different types of clinical specimens. Methods A retrospective observational study was conducted, including adult KTRs with suspected ATB from the Eighth Medical Center of Chinese People's Liberation Army General Hospital from January 2020 to January 2025. Baseline data of the recipients were collected and analyzed, and the diagnostic criteria were based on a composite reference standard (including clinical diagnosis and bacteriological confirmation). The single-detection efficacy of acid-fast staining smear, mycobacterium tuberculosis culture, Xpert test for the detection of mycobacterium tuberculosis nucleic acid and resistance to rifampicin (Xpert MTB/RIF), as well as tuberculosis or non-tuberculosis mycobacterial DNA detection was compared. The differences in sensitivity among different methods were analyzed. Results A total of 95 KTRs with suspected ATB and 136 specimens were included. And 52 cases were diagnosed as ATB, among which 48 cases were confirmed by bacteriological means (92%). The sensitivity of Xpert MTB/RIF and DNA detection (0.55 and 0.52, respectively) was significantly higher than that of acid-fast staining smear (0.30) and mycobacterium tuberculosis culture (0.35) (P < 0.01). There was a statistically significant difference in the bacteriological diagnosis rate among different specimen types (P = 0.035). The detection sensitivity of each method was the highest in pus, puncture tissue and bronchoalveolar lavage fluid, followed by sputum and pleural and abdominal effusions, and the lowest in cerebrospinal fluid. Conclusions The sensitivity of nucleic acid amplification technology for immunosuppressed KTRs is slightly reduced, but it should still be recommended as the preferred initial screening tool. The comprehensive strategy of "multi-site sampling (prior to obtaining high bacterial load specimens) combined with multiple method detection" may improve the diagnostic efficacy.

ObjectiveTo investigate the antiviral efficacy of pegylated interferon α-2b （PEG-IFN-α-2b） in patients with HBV-related liver cirrhosis， to assess the safety and tolerability of this regimen， and to provide evidence-based medical evidence for optimizing the treatment strategies for patients with HBV-related compensated liver cirrhosis. MethodsA prospective study was conducted among 115 patients with HBV-related compensated liver cirrhosis and 114 patients with CHB who attended Third People’s Hospital of Taiyuan from January 2023 to March 2024. Treatment-naïve patients received PEG-IFN-α-2b monotherapy， while the patients once treated with nucleos（t）ide analogues （NAs） received PEG-IFN-α-2b add-on therapy. The patients with HBV-related compensated liver cirrhosis were followed up at baseline and at 12， 24， 36， and 48 weeks of treatment. Samples were collected from CHB patients at baseline and at the end of follow-up to assess virological indicators， routine blood test results， and liver function. The chi-square test was used for comparison of categorical data between groups； the independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the one-way repeated measures analysis of variance was used for comparison among different time ponts within the same group，and the Bonferroni was applied for post-hoc pairwise comparisons； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Friedman test was used for comparison across different time points within the same group， and the Nemenyi test was utilized for subsequent pairwise comparisons. The multivariate stepwise Logistic regression analysis was used to investigate the influencing factors for clinical cure. ResultsCompared with the CHB group， the HBV-related compensated liver cirrhosis group had a significantly higher mean age （43.50±9.97 years vs 40.90±8.16 years， t=2.160， P=0.032）， a significantly higher proportion of patients with hepatitis B e antigen at baseline （28.70% vs 15.79%， χ²=4.788， P=0.029）， and a significantly lower platelet level ［（178.67±55.07）×10⁹/L vs （194.93±55.79）×10⁹/L， t=2.217， P=0.028］. Compared with the CHB group at the end of follow-up， the HBV-related compensated liver cirrhosis group had significantly lower HBV surface antigen （HBsAg） clearance rate （10.38% vs 33.04%， χ²=14.988， P<0.001） and HBV surface antibody positive rate （0.00% vs 19.64%， χ²=21.041， P<0.001）. Compared with the CHB group at the end of follow-up，the HBV-related compensated liver cirrhosis group had significantly lower aminotransferase levels ［ALT： 31.00（19.00～47.50） U/L vs 40.00（27.00～57.00） U/L， Z=2.433， P<0.05； AST： 31.00（23.00～45.50） U/L vs 37.00（25.00～52.00） U/L， Z=1.963， P<0.05］， but significantly higher level of white blood cells （WBC） ［（4.02±1.56）×10⁹/L vs （3.59±1.24）×10⁹/L， t=2.272， P<0.05］， neutrophils ［（2.39±1.17）×10⁹/L vs （1.87±0.94）×10⁹/L， t=3.284， P<0.05］， and platelets ［（143.93±68.10）×10⁹/L vs （121.88±49.72）×10⁹/L， t=2.588， P<0.05］. A lower level of HBsAg （OR=0.997， 95%CI： 0.996　—　0.999， P<0.001） and previous treatment with NAs （OR=5.889， 95%CI： 2.195　—　17.330， P<0.001） were positive predictive factors for clinical cure， while liver cirrhosis （OR=0.177， 95%CI： 0.063　—　0.470， P<0.001） was a negative predictive factor for clinical cure. During follow-up， no patients experienced acute decompensation or progression to hepatocellular carcinoma， and the main adverse events included fever， fatigue， reductions in WBC and platelets， weight loss， alopecia， and thyroid dysfunction. In the subgroup analysis of HBV-related compensated liver cirrhosis， in both the treatment-naïve patients and the patients previously treated with NAs， there was a significant reduction in HBsAg level from baseline to week 36 of treatment ［treatment-naïve： 99.25 （5.87　—　1 212.35） IU/mL vs 403.47 （36.94　—　2 569.02） IU/mL， P<0.05； previously treated with NAs： 205.94 （14.00　—　737.80） IU/mL vs 427.03 （65.64　—　1 552.65） IU/mL， P<0.05］ and week 48 of treatment ［treatment-naïve： 85.45 （0.58　—　827.56） IU/mL vs 403.47 （36.94　—　2 569.02） IU/mL， P<0.05； previously treated with NAs： 45.28 （0.16　—　267.27） IU/mL vs 427.03 （65.64　—　1 552.65） IU/mL， P<0.05］. There were significant increases in the levels of aminotransferases during treatment， as well as significant reductions in the levels of WBC， neutrophils， platelets， and hemoglobin （all P<0.05）. ConclusionAlthough a finite course of PEG-IFN-α-2b therapy has achieved a relatively low rate of clinical cure in the treatment of HBV-related compensated liver cirrhosis， it can still significantly reduce the level of HBsAg， and this treatment regimen has good safety and tolerability， without accelerating disease progression.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and abnormal accumulation of α‑synuclein. Its pathogenesis involves multiple interconnected processes, including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, neuroinflammation, and impaired protein homeostasis. Extracellular signal-regulated kinase 1/2 (ERK1/2), a major component of the mitogen-activated protein kinase signaling network, plays an important role in neuronal survival, synaptic plasticity, stress responses, and cell death. However, accumulating evidence indicates that ERK signaling in PD is not unidirectional, as both insufficient activity and sustained overactivation have been associated with neuronal dysfunction and disease progression. In this review, we systematically summarize the evidence for the pathological and protective roles of ERK signaling in PD. Insufficient ERK activity may impair neurotrophic support, synaptic plasticity, mitochondrial homeostasis, and neuronal adaptation to stress, thereby increasing the vulnerability of dopaminergic neurons. In contrast, persistent and excessive ERK activation may promote neuroinflammation, oxidative stress, mitochondrial dysfunction, apoptosis, autophagy-lysosomal impairment, and abnormal α-synuclein accumulation. Conversely, moderate and transient ERK activation induced by neurotrophic factors, bioactive compounds, or exercise may enhance neuronal survival, antioxidant defense, synaptic plasticity, and functional recovery. These apparently contradictory findings suggest that ERK activation itself cannot be simply classified as either neuroprotective or neurotoxic. Based on the available evidence, we propose the concept of an “ERK activity window” to explain the context-dependent effects of ERK signaling in PD. This hypothesis suggests that ERK activity needs to remain within an appropriate dynamic range to maintain neuronal homeostasis and adaptive responses. ERK activity below this range may weaken neurotrophic support and stress resistance, whereas prolonged and high-intensity activation may exceed the adaptive capacity of neurons and glial cells, thereby promoting inflammatory and degenerative processes. Importantly, this functional window should not be regarded as a fixed threshold. Its biological effects are likely determined by the intensity and duration of activation, cell type, subcellular localization, upstream stimuli, interaction with other signaling pathways, and disease stage. This framework may therefore help reconcile the apparently inconsistent findings among different PD models and experimental conditions. From a therapeutic perspective, these findings indicate that ERK should not necessarily be considered a target for simple activation or inhibition. Instead, restoring ERK signaling toward an appropriate functional state may represent a more rational strategy. Exercise is of particular interest because it can simultaneously influence neurotrophic signaling, oxidative stress, inflammation, synaptic plasticity, and ERK activity, potentially promoting adaptive remodeling of ERK signaling according to pathological conditions. Nevertheless, current evidence is predominantly derived from cellular and animal studies, and the dynamic, cell-specific, and spatial characteristics of ERK signaling remain insufficiently defined. Blood-brain barrier penetration, long-term safety, preservation of physiological ERK functions, and the lack of reliable biomarkers for monitoring brain ERK activity also limit clinical translation. Importantly, the “ERK activity window” remains a theoretical framework, and direct clinical evidence that ERK modulation can alter the progression of human PD is currently lacking. Future studies should therefore integrate longitudinal analysis, cell-specific and spatial approaches, and clinical biomarker validation to determine whether precise regulation of ERK signaling can provide a viable strategy for disease-modifying intervention in PD.

This article reports a 14-year-old boy who presented with "a nearly 7-year history of a right upper arm mass and a more than 1-year history of cervical lymphadenopathy". His main clinical manifestations included a subcutaneous mass in the right upper arm, bilateral eyelid and submandibular masses, and multiple enlarged cervical lymph nodes, accompanied by persistent peripheral blood eosinophilia. Biopsies of the right upper arm lesion and a left submandibular lymph node showed lymphoid hyperplasia with prominent eosinophilic infiltration, vascular and fibrous tissue proliferation, and eosinophilic microabscess formation in the left submandibular lymph node, confirming the diagnosis of Kimura′s disease. The lesions regressed markedly after glucocorticoid therapy but recurred after treatment discontinuation. Because the patient and his family were concerned about long-term glucocorticoid therapy, mepolizumab was subsequently administered. Peripheral eosinophil counts normalized, whereas the local tissue lesions showed limited improvement. A multidisciplinary team comprehensively evaluated the diagnosis, the need for repeat biopsy of atypical lymph nodes on imaging, the possible association between the cardiac valve abnormalities and the underlying disease, and subsequent treatment options. The patient is currently receiving methotrexate with folic acid supplementation and remains under regular follow-up. This case indicates that the diagnosis of Kimura′s disease relies on clinical manifestations and histopathological findings. Once diagnosed, comprehensive evaluation, individualized treatment, and long-term management should be implemented.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

With the increasing demand for dynamic,real-time and rapid qualitative analysis of chemical composition in areas such as emergency response and space exploration,chip-scale mass spectrometers have attracted significant attention.These devices are expected to drive the integration of mass spectrometry with micro/nano-fabrication and intelligent sensing technologies,fostering profound innovation and breakthroughs in analytical chemistry.As an excellent mass analyzer,the ion trap exhibits numerous advantages,and its miniaturization creates favorable conditions for the high-density integration of miniature mass spectrometers.However,the reduction in ion storage capacity may compromise its sensitivity and dynamic range,rendering the study of ion unidirectional ejection in highly miniaturized ion traps of significant practical importance.In this work,a research was conducted on achieving efficient ion unidirectional ejection while maintaining high mass resolution in the extremely miniature hyperbolic linear ion trap(M-HLIT)with a field radius of 1 mm,and an electric field compensation method was proposed,which combined asymmetric electrode stretching and unbalanced RF voltage to achieve high-precision optimization of the electric field composition.Simulations showed that in an ideal structure,this method achieved 100％unidirectional ejection efficiency with the mass resolution of 518,significantly outperforming traditional asymmetric structure method(365)and unbalanced voltage method(321).Following the introduction of ion ejection slots,further optimization through bidirectional stretching and electrical parameters improved the resolution to 790 while maintaining a unidirectional ejection efficiency of 93％.This method eliminated the requirement for additional excitation voltage,offering an ideal solution for the miniature mass analyzer with high detection performance of chip-level mass spectrometers.

Lentiviral vectors(LVs)are key gene delivery tools for integrating target genes into the host genome,but they may also pose risks of insertional mutagenesis.The vector copy number(VCN)in cells is critical for determining the safety of gene modification.However,the reliability and accuracy of its quantification process are influenced by multiple factors.Developing cell reference materials with specific vector copy numbers represents a viable approach to enhance the reliability and consistency of measurement results,enabling quality control of the quantification process and traceability of outcomes.However,the preparation of such reference materials faces challenges in cell sample design,preparation protocols,and advanced quantification techniques.In this study,T lymphocyte cell line Jurkat-based reference materials with LV gene copy numbers of 1 and 2 copy/cell were developed.A high-precision duplex digital polymerase chain reaction(dPCR)method was established to quantify the LV gene and endogenous genes simultaneously.Additionally,the results of dPCR were cross-validated through next-generation sequencing and flow cytometric analysis.Ultimately,confocal microscopy characterization results showed that the developed cell reference materials had intact morphology.The quantification result of VCN-1 was(1.07±0.11)copy/cell,and that of VCN-2 was(2.09±0.21)copy/cell.These cell reference materials demonstrated compliance with stability and homogeneity requirements,and could be applied for quality control throughout the VCN measurement workflow and metrological traceability,improving the accuracy,comparability,and validity of copy number measurements.

Aerosol-assisted plasma amplification laser-induced breakdown spectroscopy(LIBS)was employed for phosphorus detection in water.To address the multivariate coupling effects in LIBS and nebulization sampling system,an orthogonal experiment was employed to systematically optimize the key experimental parameters.Using the orthogonal experimental design,the parametric effects of laser energy(output voltage),signal acquisition delay,liquid velocity,and gas velocity on the signal to background ratio(SBR)of P I 213.618 nm were evaluated,and the optimal conditions were achieved,including laser energy of 86 mJ,delay time of 3 μs,gas velocity of 1.05 mL/min,and liquid velocity of 60 μL/min,which were in agreement with the control-variable optimization results.Moreover,the SBR response trends at P I 213.618 nm with all experimental parameters was strong in consistency with control-variable optimization results,which demonstrated the validity of the orthogonal array experimental design.This study established an efficient and accurate parameter optimization methodology for complex LIBS systems,significantly advancing the application of LIBS in environmental monitoring.