Objective To analyze the clinical and therapeutic characteristics of Epstein-Barr virus (EBV)-negative posttransplant lymphoproliferative disease (PTLD) with diffuse large B-cell lymphoma (DLBCL) in the context of specific cases and literature. Methods A case of EBV-negative DLBCL (GCB type) after kidney transplantation is reported. The patient was a 45-year-old male who underwent living-related kidney transplantation in 2016 and has been receiving triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and methylprednisolone since then. In 2024, the patient presented with intermittent fever, night sweats and gastrointestinal symptoms. The diagnosis was confirmed by endoscopic pathology, immunohistochemical staining and positron emission tomography/computed tomography. The R-CDOP regimen (rituximab + cyclophosphamide + liposomal doxorubicin + vincristine + dexamethasone) was used for treatment. Results The patient was diagnosed with EBV-negative DLBCL (GCB type, Ann Arbor stage Ⅳ B). After 4 cycles of R-CDOP chemotherapy, the efficacy assessment was partial remission, and the transplant kidney function remained stable. Conclusions For EBV-negative PTLD after kidney transplantation, it is necessary to break through the "virus-dependent" diagnostic thinking. In clinical practice, the focus should be on protecting the transplant kidney, and individualized treatment plans should be developed for patients.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Objective To evaluate the performance of lightweight Chinese large language models (LLMs) in answering specialized lung cancer questions, and to explore the impact of retrieval-augmented generation (RAG) on model performance. Methods Eleven lightweight Chinese LLMs with parameter sizes ranging from 7B to 32B were included. A lung cancer-specific evaluation dataset consisting of 200 questions [100 A1-type (basic knowledge) and 100 A2-type (clinical case) questions], constructed based on clinical guidelines and thoracic surgery textbooks, was used for assessment. Model performance was evaluated under two conditions (with and without RAG). Accuracy was used to assess model performance, and response latency was recorded to reflect inference efficiency. An accuracy–latency scatter plot was constructed for descriptive analysis of overall model performance. Results All models successfully completed the evaluation. With the introduction of RAG, the overall average accuracy improved from 61.68% to 76.36%. Smaller models demonstrated the most significant improvement (e.g., the accuracy of DeepSeek-7B increased from 32.50% to 60.00%, P<0.001). The average response latency increased from 12.58 s to 13.80 s. The Qwen3 series showed the best overall performance, and Qwen3-32B achieved the highest accuracy under both conditions (76.50% and 84.00%, respectively). After RAG integration, performance differences among model families were markedly reduced. Based on the accuracy-latency trade-off, Qwen3-32B achieved the best balance between accuracy and response latency under the baseline condition, whereas Qwen3-14B demonstrated superior overall performance in terms of accuracy, latency, and computational cost after RAG integration. Conclusion The integration of RAG technology improves the ability of lightweight Chinese LLMs to answer specialized lung cancer questions. Under the dual practical constraints of limited computational resources and medical data security requirements, the "lightweight model+RAG" technical framework may represent a promising deployment solution.

Objective: To investigate the associations of sleep quality and weight stigma with depressive mood among college students, so as to provide evidence for mental health promotion in higher education institutions. Methods: From September to November 2024, a stratified cluster random sampling method was used to survey 4 524 undergraduate students from the first to third year in comprehensive universities across various cities in Inner Mongolia. The χ 2 test was used to compare the detection rates of poor sleep quality, experiences of weight stigma, and depressive mood among students with different characteristics, and multivariate Logistic regression analysis was conducted to examine the independent and combined associations between sleep quality, the number of types of weight stigma experienced, and depressive mood. Results: Among students, the detection rate of poor sleep quality was 21.60%; those with experiences of weight stigma had a detection rate of 11.52%; those with depressive mood had a detection rate of 9.46%. Multivariate Logistic regression analysis showed that, compared with those who had good sleep quality, individuals with poor sleep quality were more likely to experience depressive mood [ OR (95% CI )=2.99(2.41- 3.71 )]; compared with those who had no experience of weight stigma, individuals who experienced ≥2 types of weight stigma were more likely to experience depressive mood [ OR (95% CI )=4.51(2.82-7.22)] (both P <0.01). Multivariate Logistic regression analysis, with "good sleep quality and no weight stigma experience" as the reference group, showed that all other joint groups had a higher likelihood of developing depressive mood, with the highest likelihood observed among students who had poor sleep quality and had experienced ≥2 types of weight stigma [ OR (95% CI )=14.21(6.95-29.06), P <0.01]. Conclusions Poor sleep quality and a greater number of weight stigma types are both associated with depressive mood among college students. Mental health programs in higher education institutions should simultaneously address students sleep problems and weight related adverse experiences, and implement comprehensive interventions.

Objective: To analyze the mortality trend of chronic respiratory diseases in Lianyungang City, Jiangsu Province from 2011 to 2024, and predict the mortality from 2025 to 2029, so as to provide the evidence for developing forward-looking prevention and control strategies and targeted intervention measures. Methods: Chronic respiratory disease death surveillance data in Lianyungang City from 2011 to 2024 were collected through the Jiangsu Chronic Disease Management Information Platform. The crude mortality was calculated and standardized using the data of the Sixth National Population Census in 2010. Average annual percent change (AAPC) was used to analyze the mortality trends of chronic respiratory diseases by gender, region, and age in Lianyungang City from 2011 to 2024. The GM (1,1) grey model was established using the crude mortality of chronic respiratory diseases from 2011 to 2024 to predict the crude mortality of chronic respiratory diseases from 2025 to 2029. Results: From 2011 to 2024, the crude mortality and standardized mortality of chronic respiratory diseases in Lianyungang City were 52.20/105 and 36.57/105, respectively. The crude mortality and standardized mortality were 53.14/105 and 43.79/105 in males, respectively, which were higher than 51.17/105 and 30.14/105 in females (both P<0.05). The crude mortality and standardized mortality were 55.62/105 and 39.85/105 in rural areas, respectively, which were higher than 38.11/105 and 24.15/105 in urban areas (both P<0.05). From 2011 to 2024, the standardized mortality of chronic respiratory diseases showed downward trends in the total population, males, females, urban areas, and rural areas (AAPC=-6.956%, -5.175%, -8.659%, -4.290%, and -7.369%, all P<0.05). The crude mortality of chronic respiratory diseases in the total population showed an upward trend with increasing age (P<0.05), reaching a peak of 1 371.20/105 in the ≥80 years group. The top two causes of chronic respiratory disease deaths were chronic obstructive pulmonary disease and bronchial asthma, with 31 792 cases and 3 254 cases, accounting for 82.40% and 8.43%, respectively. The GM (1,1) grey model prediction results showed that the crude mortality of chronic respiratory diseases in the total population from 2025 to 2029 would be 37.91/105, 36.32/105, 34.80/105, 33.34/105, and 31.95/105, respectively (average relative error=8.76%). Conclusions From 2011 to 2024, the mortality of chronic respiratory diseases in Lianyungang City showed a downward trend. The risk of death from chronic respiratory diseases was higher in males, rural areas, and the elderly. It is predicted that the mortality of chronic respiratory diseases will decrease year by year from 2025 to 2029.

Objective: To explore the association between health related behaviors and anxiety, depressive symptoms, and their co-occurrence among junior and senior high school students, so as to provide evidence for developing targeted mental health promotion strategies. Methods: From September to December 2023, a stratified cluster random sampling method was used to select 6 150 junior and senior high school students from 8 districts (counties) in a northwest region of China. The Generalized Anxiety Disorder-7 and Center for Epidemiologic Studies Depression Scale were used to assess anxiety and depressive symptoms, and their co-occurrence. Latent class analysis was used to identify latent classes of health related behaviors among junior and senior high school students, and Logistic regression models were used to analyze the association of the latent category of health related behaviors with anxiety and depressive symptoms, and their co-occurrence. Results: The detection rates of anxiety and depressive symptoms, and their co-occurrence were 8.0%, 22.0%, and 7.3%, respectively, among junior high school students, and 8.3%, 26.6%, and 7.6%, respectively, among senior high school students. Latent classes of health related behaviors were classified into four classes:the comprehensive high risk behavior group (586 students, 9.5%), the Internet addiction group (376 students, 6.1%), the insufficient sleep group (1 151 students, 18.7%), and the low risk behavior group (4 037 students, 65.6%). After controlling for confounding factors such as gender, ethnicity, and monitoring sites, Logistic regression model analysis showed that, compared with the low risk behavior group, the comprehensive high risk behavior group had elevated risks of anxiety and depressive symptoms, and their co-occurrence (junior high school students: OR =3.81, 5.52, 3.88; senior high school students: OR =4.57, 4.12, 5.43; all P <0.05). The Internet addiction group had elevated risks of anxiety and depressive symptoms, and their co-occurrence among junior high school students ( OR =1.89, 2.81, 1.89), and an elevated risk of depressive symptoms among senior high school students ( OR =2.41) (all P <0.05). The insufficient sleep group had an elevated risk of their co-occurrence among junior high school students ( OR =1.47), and elevated risks of anxiety and their co-occurrence among senior high school students ( OR =1.71, 1.99) (all P <0.05). Conclusion Latent classes of health related behaviors among junior and senior high school students are associated with anxiety and depressive symptoms, and their co-occurrence, as well as differences across school stages.

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors