OBJECTIVE To systematically evaluate the influencing factors affecting the poor prognosis of drug-induced liver injury （DILI） in the Chinese population， and to provide evidence-based support for early identification and interventions of DILI. METHODS Retrieved from PubMed， Medline， Embase， the Cochrane Library， CNKI， Wanfang database， China biomedical medicine database （CBM） and VIP， clinical studies （case-control studies， cohort studies） related to influencing factors for poor prognosis of DILI were collected from inception to May 31， 2025. After literature screening， data extraction and quality evaluation of included studies， meta-analysis was carried out by using RevMan 5.4 software. RESULTS A total of 17 literature were included， involving 4 078 DILI patients， of whom 673 were in the poor prognosis group and 3 405 were in the favorable prognosis group. Meta-analysis showed that history of liver disease （OR＝2.47， 95%CI was 1.61-3.78， P ＜0.001）， alcohol drinking history （OR＝1.77， 95%CI was 1.22-2.56， P ＝0.003）， Chinese herbal medicine/Chinese patent medicine （OR＝1.87， 95%CI was 1.30-2.70， P ＜0.001）， non-hepatocellular injury type （OR＝1.70， 95%CI was 1.37-2.10， P ＜0.001）， international normalized ratio （INR） elevated （OR＝2.51， 95%CI was 1.97-3.19， P ＜0.001）， and alanine transamine （ALT） elevated （OR＝1.27， 95%CI was 1.14-1.41， P ＜0.001） were risk factors of poor prognosis in DILI. Higher albumin （ALB） level （OR＝0.47， 95%CI was 0.39-0.57， P ＜0.001）， elevated prothrombin activity （PTA） （OR＝0.88， 95%CI was 0.85-0.91， P ＜0.001） and more than 2 kinds of hepatoprotective drugs （OR＝0.62， 95%CI was 0.41-0.95， P ＝0.030） were protective factors for poor prognosis of DILI. CONCLUSIONS Patients with alcohol drinking history， history of liver disease， elevated INR， elevated ALT， taking Chinese herbal medicine/Chinese patent medicine， and non-hepatocellular injury type of DILI have a greater risk of poor prognosis， and higher ALB level， higher PTA and more than 2 kinds of hepatoprotective drugs can reduce the risk of poor prognosis of DILI.

Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

Objective:To investigate effective strategies to reduce the high risk of recurrence after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with minimal residual disease(MRD)-positive B-lineage acute lymphoblastic leukemia(B-ALL).Methods:A retrospective analysis was performed for ten B-ALL patients with positive MRD before transplantation at our center from November 2022 to November 2024.There were four male patients and six female patients,with a median age of 30(7-56)years.Of all patients,four received transplantation from unrelated donors,and six received haploidentical transplantation from relatives.All ten patients received blinatumomab(28 μg/day for 14 days for patients≥45 kg;5 μg/m2/day for 14 days for patients<45 kg)and were bridged to the conditioning regimen for allo-HSCT within 7 days.Results:After treatment with blinatumomab,all ten patients achieved the clearance of MRD.After allo-HSCT,100%of the patients achieved donor hematopoietic reconstitution.The median time to neutrophil reconstitution was 12(9-22)days,and the median time to platelet reconstitution was 13.5(9-22)days.As of January 2025,the median observation time was 14(2-26)months;of all patients,two experienced recurrence,and one had positive MRD again,with a recurrence rate of 20%.Among the ten patients,nine survived and one died of disease recurrence.One patient achieved complete re-mission again after chimeric antigen receptor T-cell(CAR-T)therapy following recurrence,and the patient with positive MRD achieved the clearance of MRD again after interleukin-2 treatment;both patients were currently alive.During treatment,one patient developed cytokine release syndrome,one patient was comorbid with SARS-CoV-2 infection,one patient had herpes zoster and viral encephalitis,three patients developed grade Ⅰ-Ⅱ acute graft-versus-host disease,and four patients developed chronic graft-versus-host disease;no transplantation-associated thrombotic microangiopathy was observed.Conclusion:For patients with MRD-positive B-ALL,blinatumomab as a bridge therapy for allo-HSCT can significantly reduce recurrence after transplantation,with fewer complica-tions that are easy to control.Multicenter randomized controlled clinical studies can be performed to further verify its efficacy and safety.

To identify factors associated with the recurrence of polymyalgia rheumatica(PMR) within one year.

Mitochondrial and peroxisome fission deficiency-related encephalopathy caused by DNM1L gene mutation is a rare and fatal epileptic encephalopathy, with clinical phenotype and genetic heterogeneity. The acute stage is drug-resistant epilepsy with poor prognosis and serious neurological sequelae. A case of genetically confirmed encephalopathy related to mitochondrial and peroxisome fission defects is reported, the clinical data, treatment process are summarized, and the previous literature is reviewed to improve the understanding of the rare disease.

Evidence-based medicine (EBM) is a science that uses the best available research data to make decisions, and the core is that clinical decision-making is supported by the best research evidence. Incorporating EBM into traditional standardized residency training in hematology can foster residents' professional theoretical knowledge and clinical skills, improve the quality of standardized training, and provide ideas and methods for standardized training of hematology residents, which is worthy of further research and exploration.

Objective:To investigate the clinical characteristics and risk factors of multiple tophi among gout patients.Methods:Gout patients treated at Affiliated Hospital of Qingdao University from September 2017 to September 2021 were included retrospectively. According to the number of tophi, the patients were divided into the multiple tophi group, the single tophi group and the non-tophi group. Clinical data were collected, biochemical indices and urine pH value were determined. One- way ANOVA or Chi-square test was used to compare groups, and multivariate logistic regression was used to analyze the risk factors. Results:The age, disease course, blood pressure, serum uric acid, urea nitrogen, and the rate of family history, smoking, drinking, gout attacks≥2 twice per year, hypertension, cardio-cerebrovascular diseases, kidney stones in the multiple tophi group were significantly higher than those in the single tophi group and the non-tophi group. The glomerular filtration rate, urine pH value and the rate of regular exercise were significantly lower than those of single tophi group and non-tophi group. In the multiple tophi group, 245 cases(44.46%) were involved in the interphalangeal joint or metacarpophalangeal joint, 212 cases(38.47%) were involved in other joints of the upper limb, which was second only to the first metatarsophalangeal joint(349 cases, 63.33%). Logistic regression analysis showed that the course of disease, urea nitrogen, serum uric acid, positive family history, drinking, gout attacks ≥twice per year and hypertension were the risk factors for multiple tophi in gout patients. Conclusion:Patients with a long disease course, elevated uric acid, high urea nitrogen, positive family history, alcohol consumption, frequent gout flare and hypertension are more likely to develop multiple tophi.

Objective:To identify the genetic variation in a mucopolysaccharidosis type Ⅱ(MPS Ⅱ)family, and conduct a functional study of iduronate-2-sulfatase(IDS): c.323A>C.Methods:A five-generation MPS Ⅱ family of 83 individuals including 4 patients from northern China was collected. Urine mucopolysaccharide and Alder-Reilly body were tested to assist the clinical diagnosis of MPS Ⅱ. IDS enzyme activity was detected on core family members. By the whole exome sequencing of a MPS Ⅱ patient in this family and bioinformatics analysis, the variant was screened and further identified by PCR-Sanger sequencing. Finally, to validate the function of the variant in vitro, the wild-type IDS overexpression plasmid(pCMV-hIDS-WT)and the IDS overexpression plasmid carrying the mutation site(pCMV-hIDS-c.323A>C)were transfected into COS-7 cells and the IDS activity was detected. Results:The proband(Ⅳ3)and Ⅳ4 were diagnosed as MPS Ⅱ by urine mucopolysaccharide, Alder-Reilly body, and IDS enzyme activity tests. Ⅳ3, Ⅳ4, Ⅲ19, and Ⅲ32 were determined to carry IDS: c.323A>C missense variant through the whole-exome sequencing, and diagnosed as MPS Ⅱ. Meanwhile, Ⅱ2, Ⅱ4, Ⅱ8, Ⅱ12, Ⅱ14, Ⅲ5, Ⅲ7, Ⅳ14 in the MPS Ⅱ family carried IDS: c.323A>C missense variant, and were excluded as MPS Ⅱ. The in vitro experiment in COS-7 cells showed that the missense mutation led to a significant decrease in IDS enzyme activity. Conclusion:The variant IDS: c.323A>C: p.Y108S significantly decreases the activity of IDS enzyme in vivo and in vitro, and it is identified as a pathogenic variant for MPS Ⅱ.

Objective:To investigate the effect of digoxin on bleomycin-induced pulmonary fibrosis in mice, and investigate its possible mechanism through in vitro and in vivo experiments. Methods:① In vivo experiment: 60 C57/BL6J mice were randomly divided into control group, pulmonary fibrosis model group (model group), pirfenidone (300 mg/kg) group, digoxin 1.0 mg/kg and 0.2 mg/kg groups, with 12 mice in each group. The pulmonary fibrosis model of mice was reproduced by single intratracheal infusion of bleomycin (5 mg/kg). The control group was given the same amount of sterile normal saline. From the next day after modeling, each group was received corresponding drugs by intragastric administration once a day for 28 days. Control group and model group were given the same amount of normal saline. The mice were sacrificed and the lung tissue was collected to detect the lung coefficient. After hematoxylin-eosin (HE) and Masson staining, the lung tissue morphology and collagen changes were observed under light microscope. Immunohistochemistry was used to detect the positive expressions of α-smooth muscle actin (α-SMA) and extracellular matrix (ECM) collagen (COL-Ⅰ and COL-Ⅲ) in lung tissue. The protein expressions of ECM fibronectin (FN), transforming growth factor-β (TGF-β) and phosphorylation of Smad3 (p-Smad3) in lung tissue were detected by Western blotting. ② In vitro experiment: human embryonic lung fibroblast-1 (HFL-1) cells were cultured and divided into blank control group, fibroblast activation model group (model group), pirfenidone (2.5 mmol/L) group and digoxin 100 nmol/L and 50 nmol/L groups when cell density reached 70%-90%. After 3-hour treatment with corresponding drugs, except blank control group, the other groups were treated with TGF-β for 48 hours to establish fibroblast activation model. The expressions of α-SMA, FN and p-Smad3 proteins and the phosphorylations of phosphatidylinositol-3-kinase (PI3K)/Akt pathway proteins PI3K and Akt (p-PI3K, p-Akt) were detected by Western blotting. Results:① In vivo, compared with the control group, the alveolar structure of mice in the model group was significantly damaged, a large number of inflammatory cells infiltrated, collagen deposition in the lung interstitium was increased, the deposition of ECM in the lung tissue was also increased, and the expressions of α-SMA, FN, TGF-β and p-Smad3 protein were increased, indicating that the model of bleomycin-induced pulmonary fibrosis in mice was successfully prepared. Compared with the model group, digoxin significantly inhibited airway inflammation and collagen fiber deposition, reduced ECM deposition, and decreased the protein expressions of α-SMA, FN, TGF-β and p-Smad3, while the effect was better than that of the pirfenidone group, and the digoxin 1.0 mg/kg group had a better effect except FN [α-SMA ( A value): 5.37±1.10 vs. 9.51±1.66, TGF-β protein (TGF-β/GAPDH): 0.09±0.04 vs. 0.33±0.23, p-Smad3 protein (p-Smad3/GAPDH): 0.05±0.01 vs. 0.20±0.07, all P < 0.01]. ② In vitro, compared with the blank control group, the expressions of FN, α-SMA, p-Smad3 and PI3K/Akt signaling proteins in the model group were increased, indicating that the fibroblast activation model induced by TGF-β was successfully reproduced. Compared with the model group, digoxin significantly inhibited fibroblast activation, and decreased the expressions of FN, α-SMA, p-Smad3, and PI3K/Akt pathway proteins, moreover, the effect was better than that of the pirfenidone group, and decreased FN, SMA and p-Akt protein expressions were more obvious in digoxin 100 nmol/L group [FN protein (FN/GAPDH): 0.21±0.15 vs. 0.88±0.22, α-SMA protein (α-SMA/GAPDH): 0.20±0.01 vs. 0.50±0.08, p-Akt protein (p-Akt/GAPDH): 0.30±0.01 vs. 0.65±0.10, all P < 0.01]. Conclusion:Digoxin could suppress the pulmonary fibrosis in mice induced by bleomycin, which might be associated with the regulation of fibroblast activation via suppressing PI3K/Akt signaling pathway in a dose-dependent manner.

Objective:To analyze the clinical characteristics and risk factors associated with the formation of subcutaneous tophi among young gout patients.Methods:Gout patients treated at the Affiliated Hospital of Qingdao University from September 2016 to June 2020 were included. The clinical information was collected and relevant biochemical indices were detected. Fasting urine was collected to test urine pH value, urine uric acid and urine creatinine. Patients were divided into young tophi group and non-tophi group according to age. The measurement data of normal distribution was expressed as Mean±Standard deviation, and independent sample t test and one-way analysis of variance were used. The counting data was tested by Chi-square test. The risk factors were analyzed by logistic regression. Results:A total of 4 798 primary gout patients were collected. There were 915 patients with subcutaneous tophi, 2 308 young gout patients, 252 young gouty tophi patients among them. The average BMI, waist circumference, hip circumference, triglyceride level, serum uric acid level, glomerular filtration rate, alanineamino -transferase (ALT) and aspartate amino -transferase (AST) in the young tophi group were significantly higher than those in the middle-age tophi group ( F=46.074, 2.551, 9.203, 10.370, 15.118, 68.741, 35.023, 5.175, all P<0.05). Average age of disease onset, systolic blood pressure, fasting blood glucose, urine FEUA, Uua/Ucr and urea nitrogen level in young tophi group were significantly lower than those in middle-age tophi group ( F=474.876, 7.629, 6.441, 34.877, 3.633, 50.867, all P<0.05]. The age [(35±7) years old vs (33±7) years old], disease course [(7±4) years vs (4±3) years], blood pressure [(139±17) mmHg vs (135±16) mmHg], [(90±13) mmHg vs (86±12) mmHg], serum triglyceride [(2.6±2.1) mmol/L vs (2.4±2.0) mmol/L], total cholesterol [(4.9±1.4) mmol/L vs (4.6±1.4) mmol/L], serum uric acid [(547±171) μmol/L vs (490±160) μmol/L], urea nitrogen [(5.0±2.0) mmol/L vs (4.4±1.7) mmol/L], family history (27.0% vs 19.6%) and smoking rate(56.0% vs 48.9%) of tophi patients were significantly higher than those of non-tophi patients in young patients ( t=4.717, P<0.05; t=12.838, P<0.05; t=3.414, P<0.05; t=4.676, P<0.05; t=2.085, P<0.05; t=2.451, P<0.05; t=5.308, P<0.05; t=4.090, P<0.05; χ2=7.423, P<0.05; χ2=4.235, P<0.05) . The age of disease onset [(28±6) years vs (29±7) years] and glomerular filtration rate [(96±21) ml·min -1·1.73 m -2vs (103±21) ml·min -1·1.73 m -2] were statistically significantly lower than those of non-tophi patients ( t=-2.711, P<0.01; t=-4.907, P<0.01). Logistics regression analysis showed that age, course of disease, blood pressure, blood lipids level, serum uric acid level, family history of gout and smoking were risk factors for the formation of tophi in young people. After further adjusted for age, course of disease and family history of gout, it was found that serum uric acid, systolic blood pressure, diastolic blood pressure and urea nitrogen remined risk factors for tophi, while glomerular filtration rate remained a protective factor in young patients. Conclusion:Young tophi patients are always obese and have lipid metabolism disorder. Young patients with high level of serum uric acid and blood pressure, decreased renal function are prone to complicate with subcutaneous tophi. More attention should be paid in clinical practice to prevent or delay the formation of tophi.