To investigate the efficacy and safety of glucocorticoids combined with cyclophosphamide (CTX) and rituximab (RTX) in elderly patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement.

This article reports a case of an elderly male patient presenting with nephrotic syndrome. Renal biopsy pathology indicated membranous nephropathy, with both renal tissue staining for M-type phospholipase A2 receptor (PLA2R) and serum anti-PLA2R antibodies being negative. Nephrotic syndrome achieved remission following treatment with prednisone combined with tacrolimus; however, the patient relapsed during tacrolimus maintenance therapy. Subsequent laboratory evaluation revealed positive anti-nuclear antibodies and anti-double-stranded DNA antibodies, accompanied by decreased complement levels. Exostosin 1 and Exostosin 2 staining performed on the initial renal biopsy specimen yielded positive results, leading to a diagnosis of lupus nephritis. Due to the patient's history of rituximab-related allergic reactions, pulmonary infection, and acute kidney injury, the subsequent treatment regimen consisted of obinutuzumab sequentially combined with belimumab, in addition to prednisone 10 mg/d. During the two-year follow-up period, the patient's anti-double-stranded DNA antibodies converted to negative, complement levels normalized, proteinuria achieved complete remission, and no adverse events such as severe infection occurred. This article reviews the diagnosis, treatment, and relevant literature for this case, aiming to provide clinical insights for the early diagnosis and selection of therapeutic strategies for similar patients.

OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

Objective: To evaluate the efficacy and safety of ruxolitinib combined with low-dose hormone for patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Thirty patients with aGVHD after allo-HSCT admitted to the Department of Hematology of the General Hospital of Western Theater Command from November 2021 to November 2024 were retrospectively analyzed. All patients were treated with low-dose hormone (methylprednisolone 0.3-1 mg kg -d ) combined with ruxolitinib 5-10 mg d . The efficacy and adverse reactions were observed during the follow-up period to analyze the survival outcomes of the patients. Results: A total of 30 patients with aGVHD after allo-HSCT were included in this study, consisting of 15 (50%) males and 15 (50%) females with a median age of 34 year-old (ranging from 14 to 62). Classification by disease type: there were 18 cases of acute myeloid leukemia, 4 cases of acute lymphoblastic leukemia, 4 cases of aplastic anemia, and 4 cases of myelodysplastic syndrome. Classification by aGVHD severity: there were 27 cases (90%) of Ⅱ-Ⅳ degree aGVHD and 11 cases (36.7%) of Ⅲ-Ⅳ degree aGVHD. Ruxolitinib in combination with low-dose glucocorticoid treatment yield responses in 28 (93.3%) patients, of which 27 (90%) achieved complete remission (CR), while 1 (3.3%) showed partial remission (PR). One patient (3.3%) had no response (NR), and 1 patient (3.3%) exhibited progressed disease (PD). Overall survival (OS) at 1 year of transplantation was 73.9% (95%CI 49.5% to 87.7%), progression-free survival (PFS) was 93.3% (95%CI 75.9% to 98.3%), non-relapse mortality (NRM) was 20.6% (95%CI 7.9% to 47.4%), and median survival time was 27.6 months. Conclusion: Ruxolitinib combined with low-dose hormones is safe and effective in the treatment of aGVHD after allo-HSCT.

In this paper， by referring to ancient and modern literature， the textual research of Inulae Flos has been conducted to clarify the name， origin， production area， quality evaluation， harvesting， processing and others， so as to provide reference and basis for the development and utilization of famous classical formulas containing this herb. After textual research， it could be verified that the medicinal use of Inulae Flos was first recorded in Shennong Bencaojing of the Han dynasty. In successive dynasties， Xuanfuhua has been taken as the official name， and it also has other alternative names such as Jinfeicao， Daogeng and Jinqianhua. The period before the Song and Yuan dynasties， the main origin of Inulae Flos was the Asteraceae plant Inula japonica， and from the Ming and Qing dynasties to the present， I. japonica and I. britannica are the primary source. In addition to the dominant basal species， there are also regional species such as I. linariifolia， I. helianthus-aquatili， and I. hupehensis. The earliest recorded production areas in ancient times were Henan， Hubei and other places， and the literature records that it has been distributed throughout the country since modern times. The medicinal part is its flower， the harvesting and processing method recorded in the past dynasties is mainly harvested in the fifth and ninth lunar months， and dried in the sun， and the modern harvesting is mostly harvested in summer and autumn when the flowers bloom， in order to remove impurities， dry in the shade or dry in the sun. In addition， the roots， whole herbs and aerial parts are used as medicinal materials. In ancient times， there were no records about the quality of Inulae Flos， and in modern times， it is generally believed that the quality of complete flower structure， small receptacles， large blooms， yellow petals， long filaments， many fluffs， no fragments， and no branches is better. Ancient processing methods primarily involved cleaning， steaming， and sun-drying， supplemented by techniques such as boiling， roasting， burning， simmering， stir-frying， and honey-processing. Modern processing focuses mainly on cleaning the stems and leaves before use. Regarding the medicinal properties， ancient texts describe it as salty and sweet in taste， slightly warm in nature， and mildly toxic. Modern studies characterize it as bitter， pungent， and salty in taste， with a slightly warm nature. Its therapeutic effects remain consistent across eras， including descending Qi， resolving phlegm， promoting diuresis， and stopping vomiting. Based on the research results， it is recommended that when developing famous classical formulas containing Inulae Flos， either I. japonica or I. britannica should be used as the medicinal source. Processing methods should follow formula requirements， where no processing instructions are specified， the raw products may be used after cleaning.

In this paper， by referring to ancient and modern literature， the textual research of Inulae Flos has been conducted to clarify the name， origin， production area， quality evaluation， harvesting， processing and others， so as to provide reference and basis for the development and utilization of famous classical formulas containing this herb. After textual research， it could be verified that the medicinal use of Inulae Flos was first recorded in Shennong Bencaojing of the Han dynasty. In successive dynasties， Xuanfuhua has been taken as the official name， and it also has other alternative names such as Jinfeicao， Daogeng and Jinqianhua. The period before the Song and Yuan dynasties， the main origin of Inulae Flos was the Asteraceae plant Inula japonica， and from the Ming and Qing dynasties to the present， I. japonica and I. britannica are the primary source. In addition to the dominant basal species， there are also regional species such as I. linariifolia， I. helianthus-aquatili， and I. hupehensis. The earliest recorded production areas in ancient times were Henan， Hubei and other places， and the literature records that it has been distributed throughout the country since modern times. The medicinal part is its flower， the harvesting and processing method recorded in the past dynasties is mainly harvested in the fifth and ninth lunar months， and dried in the sun， and the modern harvesting is mostly harvested in summer and autumn when the flowers bloom， in order to remove impurities， dry in the shade or dry in the sun. In addition， the roots， whole herbs and aerial parts are used as medicinal materials. In ancient times， there were no records about the quality of Inulae Flos， and in modern times， it is generally believed that the quality of complete flower structure， small receptacles， large blooms， yellow petals， long filaments， many fluffs， no fragments， and no branches is better. Ancient processing methods primarily involved cleaning， steaming， and sun-drying， supplemented by techniques such as boiling， roasting， burning， simmering， stir-frying， and honey-processing. Modern processing focuses mainly on cleaning the stems and leaves before use. Regarding the medicinal properties， ancient texts describe it as salty and sweet in taste， slightly warm in nature， and mildly toxic. Modern studies characterize it as bitter， pungent， and salty in taste， with a slightly warm nature. Its therapeutic effects remain consistent across eras， including descending Qi， resolving phlegm， promoting diuresis， and stopping vomiting. Based on the research results， it is recommended that when developing famous classical formulas containing Inulae Flos， either I. japonica or I. britannica should be used as the medicinal source. Processing methods should follow formula requirements， where no processing instructions are specified， the raw products may be used after cleaning.

To summarize the clinical experience of treating idiopathic olfactory disorder from the perspective of heart and lungs. It is believed that the sense of olfaction is based on the nose， rooted in the heart， functioning through the lungs， and conveyed by pectoral qi. The key pathogenesis of idiopathic olfactory disorder lies in the accumulation of pathogenic factors in the heart and lungs， blood vessel obstruction， the failure of the lungs to disperse and descend， and the loss of control of pectoral qi. In treatment， internal and external therapies could be combined. The internal therapy can correct the imbalance of the zang-fu organs， using the self-prescribed Bilong Formula （鼻聋方） to dispel wind and diffuse the lung， invigorate blood and relieving stuffy orifices； the external therapy can clear nasal obstruction， supplemented by intradermal needle embedding at three acupoints， bilateral Yingxiang （LI 20）， bilateral Shangyingxiang （EX-HN 8） and Yintang （GV 29）， and integrated olfactory training for comprehensive treatment.

OBJECTIVE To explore the risk factors for acute kidney injury （AKI） in children with steroid-resistant nephrotic syndrome （SRNS） during tacrolimus treatment and construct a predictive model. METHODS A retrospective selection was made of 155 children diagnosed with SRNS and treated with tacrolimus at Xuzhou Children’s Hospital from January 1， 2022， to December 31， 2023， serving as the study subjects. Various clinical data of the children were collected by reviewing the medical record system. Children who developed AKI during medication were assigned to the AKI group （n＝26）， and those who did not develop AKI were assigned to the control group （n＝129）. Univariate and multivariate Logistic regression analyses were used to screen independent risk factors. A clinical predictive model was constructed based on significant variables， and nomogram， calibration curve， receiver operator characteristic curve， and decision curve were drawn to evaluate the model’s performance. RESULTS Univariate analysis showed that blood urea nitrogen （BUN）， serum creatinine （Scr）， estimated glomerular filtration rate （eGFR）， the maximum trough concentration （cmin） of tacrolimus， CYP3A5*3/*3 genotype， concurrent infection， concurrent hypertension， and the use of non-steroidal anti-inflammatory drugs were influencing factors for AKI in children with SRNS during tacrolimus treatment （P＜0.05）. Multivariate Logistic regression analysis revealed that BUN≥9.58 mmol/L， Scr≥125 μmol/L， eGFR＜37 mL/（min·1.73 m2）， tacrolimus maximum cmin≥11.26 ng/mL，CYP3A5*3/*3 genotype， concurrent infection， and concurrent hypertension were independent risk factors for AKI in children with SRNS during tacrolimus treatment （P＜0.05）. The constructed clinical predictive model had an area under the curve of 0.747， showing good agreement between predicted and actual AKI occurrence and demonstrating favorable clinical net benefit in predicting AKI in children. CONCLUSIONS Impaired baseline renal function （elevated BUN， elevated Scr， and decreased eGFR）， elevated maximum cmin of tacrolimus， CYP3A5*3/*3 genotype， concurrent infection， and hypertension during treatment are independent risk factors for AKI in children with SRNS during tacrolimus treatment. The established clinical predictive model provides a scientific basis for implementing risk stratification management.

Core fucosylation, catalyzed exclusively by fucosyltransferase 8 (FUT8), is an evolutionarily conserved post-translational modification that has emerged as a central regulatory hub linking liver homeostasis, chronic disease progression, and malignant transformation. Liver diseases, particularly hepatocellular carcinoma, remain a leading global health burden characterized by late diagnosis, limited therapeutic options, and poor overall survival. While aberrant glycosylation is now recognized as a hallmark of cancer and inflammatory disorders, existing research on FUT8-mediated core fucosylation in liver diseases remains fragmented: the dynamic functional switch of FUT8 from a homeostatic regulator to a pathological driver across the full disease continuum has not been systematically delineated, and the integrated mechanisms by which core fucosylation modulates oncogenic signaling, metabolic reprogramming, and immune evasion remain poorly understood. This review synthesizes recent advances to establish a unified framework for understanding the dual role of core fucosylation in liver physiology and pathology, and evaluates its translational potential for precision medicine. At the molecular level, FUT8’s unique catalytic specificity makes core fucosylation an irreplaceable modification, as evidenced by the perinatal lethality and severe organ dysfunction in Fut8 knockout mice. In hepatocellular carcinoma, genomic amplification of guanosine 5'-diphosphate-fucose biosynthetic enzymes provides metabolic support for aberrant core fucosylation. FUT8 expression is tightly regulated by a multi-layered network: transcriptional activation via Wnt/β‑catenin and wild-type p53, epigenetic upregulation by lncRNAs, post-transcriptional repression by miR-122-5p and miR-34a, and virus-specific induction by hepatitis B virus/hepatitis C virus. Physiologically, core fucosylation maintains liver homeostasis through four core mechanisms: it acts as a molecular switch for epidermal growth factor receptor/hepatocyte growth factor receptor signaling to enable liver regeneration; directs polarized secretion of hepatocyte-derived glycoproteins into bile ducts; modulates cholesterol metabolism via the hepatocyte nuclear factor 1α-proprotein convertase subtilisin/kexin type 9-low density lipoprotein receptor axis; and regulates aging through insulin‑like growth factor 1 receptor signaling. Pathologically, core fucosylation exhibits context-dependent dual functions: in liver fibrosis, FUT8 upregulation in hepatic stellate cells forms a negative feedback loop that limits excessive fibrogenesis; in hepatocellular carcinoma, however, aberrant FUT8 overexpression drives cell-autonomous malignancy by constitutively activating epidermal growth factor/hepatocyte growth factor receptor, transforming growth factor‑β/Smad, and Wnt/β‑catenin pathways, while simultaneously establishing a multi-layered immune evasion network by stabilizing programmed cell death ligand 1 and cluster of differentiation 47, and impairing natural killer cell homeostasis via interleukin‑2 receptor β glycosylation. Clinically, stage-specific core fucosylation biomarkers enable non-invasive monitoring of liver disease progression: low molecular mass kringle-Fc fusion protein outperforms conventional markers for early fibrosis detection, while alpha-fetoprotein-L3 and novel glycopeptides (α‑2‑macroglobulin N‑linked glycosylation site 1424, lumican core fucosylated peptide) significantly improve early hepatocellular carcinoma diagnosis, especially in alpha-fetoprotein-negative patients. Next-generation detection technologies (chemoenzymatic labeling, site-specific mass spectrometry) overcome the specificity limitations of traditional lectin assays. Therapeutically, four promising strategies are emerging: small-molecule FUT8 inhibitors, afucosylated antibodies with enhanced antibody‑dependent cellular cytotoxicity, Fuc-modified targeted drug delivery systems, and core fucose-specific lectins for NASH treatment. The core challenge for clinical translation lies in FUT8’s inherent “double-edged sword” effect, as systemic inhibition disrupts its essential physiological functions beyond pathological roles. Long-term systemic FUT8 blockade not only impairs post-injury liver regeneration by abrogating epidermal growth factor/hepatocyte growth factor receptor signaling but also disrupts cholesterol homeostasis via the hepatocyte nuclear factor 1α-proprotein convertase subtilisin/kexin type 9-low density lipoprotein receptor axis, leading to dyslipidemia and altered bile secretion. Critically, it compromises immune surveillance by destabilizing interleukin‑2 receptor β on natural killer cells, reducing their cytotoxic activity against malignant and virally infected cells, and impairs IgG Fc-mediated effector functions, increasing susceptibility to infections. This fundamental trade-off between therapeutic efficacy and systemic toxicity necessitates a paradigm shift from non-specific global inhibition to precision modulation of pathological core fucosylation. By addressing these critical challenges, FUT8-mediated core fucosylation has the potential to transform liver disease management from late-stage intervention to early detection and precision therapy, ultimately improving patient outcomes and reducing the global burden of liver diseases.

[摘 要] 目的：探讨年轻乳腺癌独特的DNA甲基化特征，筛选与预后相关的甲基化位点，构建并验证预后预测模型，并通过多组学整合及关键蛋白验证评估其临床价值。方法：收集癌症基因组图谱（TCGA）数据库中的乳腺癌样本DNA甲基化及临床数据，筛选年轻乳腺癌特有的甲基化位点。采用随机森林、LASSO回归及单因素和多因素Cox比例风险回归分析构建预后模型。使用受试者工作特征（ROC）曲线、校准曲线和一致性指数（C-index）评估模型性能，并比较高、低风险组间的多组学特征差异，在独立队列中通过免疫组化法检测模型关键基因LAMA5的蛋白表达，分析其与预后的关系。结果：年轻乳腺癌相较于老年乳腺癌，在启动子区域（尤其是CpG岛）呈现显著低甲基化特征。通过多步骤差异分析获得3 489个年轻乳腺癌特有的甲基化位点，经Cox比例风险回归筛选出12个与总生存期（OS）独立相关的位点，其中启动子区、基因体区和基因间区位点各4个。基于筛选出的12个甲基化位点构建的预测模型，在TCGA训练集中显示出良好的区分度，高风险组总生存期显著更差（P = 0.002 5），5、8和10年OS预测曲线下面积（AUC）达0.88～0.94。多组学分析显示，高风险组丝裂原活化蛋白激酶（MAPK）信号通路激活，TP53基因突变频率更高，雌激素受体α蛋白表达较低。将TP53突变状态及雌激素受体1（ESR1）mRNA表达水平等关键多组学指标纳入模型，构建综合列线图，其预测效能进一步提升。组织芯片验证显示，模型关键基因LAMA5蛋白表达阴性患者的OS更差（P = 0.046），且富集于三阴性乳腺癌，与模型高风险组的临床病理特征一致。结论：整合启动子和非启动子区域信息的基于12个甲基化位点的模型可用于年轻乳腺癌患者的预后分层。联合年龄、TP53突变及ESR1 mRNA表达水平构建的综合列线图显示出较单一甲基化模型更高的预测效能。