1.Establishment and Evaluation of New Mouse Model of Rheumatoid Arthritis Combined with Interstitial Lung Disease
Liting XU ; Qingyu ZHAO ; Chao YANG ; Lianhua HE ; Congcong SUN ; Shuangrong GAO ; Lili WANG ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):81-90
ObjectiveTo establish a mouse model of rheumatoid arthritis with interstitial lung disease (RA-ILD) in DBA/1 mice using Porphyromonas gingivalis (Pg) infection combined with collagen-induced arthritis (CIA), and to comprehensively evaluate pathological characteristics in joints, lungs, and serum. MethodsForty DBA/1 mice were randomly divided into four groups, i.e., Control, Pg infection (Pg), CIA, and Pg infection combined with CIA (Pg+CIA), with 10 mice in each group. Arthritis clinical symptoms were evaluated by recording arthritis incidence and clinical scores. Micro-CT scanning was used to assess knee joint pathology. Histopathological changes and collagen deposition in knee joints and lung tissues were analyzed using hematoxylin-eosin (HE) and Masson staining. Immunohistochemistry was performed to detect protein expression of α-smooth muscle actin (α-SMA), typeⅠ collagen (ColⅠ), and fibronectin (FN) in lung tissues. Real-time quantitative polymerase chain reaction(Real-time PCR)was used to measure mRNA expression levels of α-SMA, ColⅠ, FN, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β in lung tissues. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of Pg, cyclic citrullinated peptide (CCP), and immunoglobulin G (IgG). ResultsJoint lesions: The CIA and Pg+CIA groups showed 100% arthritis incidence, with evident joint redness, swelling, and deformity. The number of affected limbs was 27 and 28, and clinical scores were 68 and 70, respectively. No obvious clinical symptoms were observed in the Pg group. Histopathological and imaging analyses showed severe joint lesions in the CIA and Pg+CIA groups, with significantly increased histopathological scores, bone mineral density, bone volume fraction, trabecular thickness, and trabecular number compared to the Control group (P<0.01). No obvious joint pathology was observed in the Pg group. Lung lesions: The Pg+CIA group exhibited marked alveolar inflammation, interstitial inflammatory cell infiltration, and alveolar wall thickening, with pronounced blue staining of collagen fibers. Histopathological scores and collagen area ratios were significantly higher than those of the Control, Pg, and CIA groups (P<0.05). Lung protein and mRNA expression levels of α-SMA, ColⅠ, and FN were markedly increased, and mRNA levels of IL-6, TNF-α, and IL-1β were significantly elevated compared to the Control group (P<0.05). Serology: The Pg+CIA group showed significantly higher levels of CCP, Pg, and IgG compared with the Control, Pg, and CIA groups (P<0.05). ConclusionDBA/1 mice subjected to Pg infection combined with CIA exhibited pronounced symptoms and pathological features of RA-ILD, along with elevated serum anti-CCP antibody levels. This model represents a novel RA-ILD mouse model, providing a valuable experimental tool for investigating RA-ILD pathogenesis and developing new therapeutics, and serves as a basis for establishing anti-cyclic citrullinated peptide antibody (ACPA)-positive RA-ILD animal models.
2.Introduction and enlightenment of the Recommendations and Expert Consensus for Plasma and Platelet Transfusion Strategies in Critically Ill Children Following Severe Trauma, Traumatic Brain Injury, and/or Intracranial Hemorrhage: From the Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding
Zhenzhen JIANG ; Rong GUI ; Rong HUANG ; Junhua ZHANG ; Jiaohui ZENG ; Hao TANG ; Zhi LIN ; Dan WAN ; Mingyi ZHAO ; Minghua YANG ; Lan GU ; Haiting LIU
Chinese Journal of Blood Transfusion 2026;39(2):285-293
Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding developed a strategy for platelet and plasma infusion management in critically ill children based on systematic reviews and consensus meetings of international multidisciplinary experts. One good practice statement and six expert consensus statements were proposed for plasma and platelet transfusions in critically ill children following severe trauma, traumatic brain injury, and/or intracranial hemorrhage. This article introduces the specific methods and basis for the formation of recommendations in this part of the guide.
3.Expert consensus on clinical application of parenteral direct thrombin inhibitors in perioperative period
Mingyu JIANG ; Yuan BIAN ; Lizhu HAN ; Qinan YIN ; Fengjiao KANG ; Anhua WEI ; Danjie ZHAO ; Lin WANG ; Ying SHAO ; Li TANG ; Yi WANG ; Shuhong LIANG ; Huijuan LIU ; Guirong XIAO ; Yue LI
China Pharmacy 2026;37(6):689-699
OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors (DTIs) in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital (the Affiliated Hospital of UESTC), a multidisciplinary working group was established. Through literature review and the Delphi method, clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework; systematic searches were conducted in CNKI, Medline, Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment,Development and Evaluation (GRADE) approach, and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations (each with an expert consensus rate exceeding 90%) on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection, dosing ranges, key monitoring points, and safety management strategies for parenteral DTIs in various scenarios, including the perioperative period of ventricular assist device implantation, the perioperative period of cardiac surgery, perioperative patients with lower-extremity atherosclerotic disease, the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome, the perioperative period of carotid artery stenting in patients with carotid stenosis, the perioperative period of patients with right heart thrombosis, and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition, warning and management pathways for perioperative bleeding and thrombotic events were proposed. 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 perioperative period.
4.Clinical comprehensive evaluation of four nucleoside (acid) analogues in the treatment of chronic hepatitis B
Jiayi QIN ; Kuifen MA ; Wenya SHAN ; Lijuan ZHAO ; Lin LIU ; Liangping WANG
China Pharmacy 2026;37(7):859-863
OBJECTIVE To conduct a comprehensive clinical evaluation of four nucleoside (acid) analogues that have been approved and marketed in China, such as entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, and tenofovir amibufenamide. METHODS According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs (2021 edition, trial implementation), a comprehensive search was conducted across databases including CNKI, Wanfang Data, VIP, PubMed, the Cochrane Library, Embase, as well as relevant official websites. Drug package inserts, guidelines, consensus statements, and relevant literature for the four drugs were collected and subjected to a comprehensive evaluation across six dimensions: safety, efficacy, cost-effectiveness, innovativeness, suitability, and accessibility. RESULTS The scores for entecavir in terms of safety, efficacy, cost-effectiveness, innovativeness, suitability, and accessibility-along with its comprehensive score-were 13, 14, 13, 10, 18, and 6, totaling 74 points. For tenofovir disoproxil fumarate, the respective scores were 13, 17, 18, 8, 18, and 7, totaling 81 points. For tenofovir alafenamide fumarate, the scores were 14, 20, 12, 8, 18, and 5, totaling 77 points. Finally, for tenofovir amibufenamide, the scores were 10.5, 17, 10, 6, 15, and 4, totaling 62.5 points. CONCLUSIONS Tenofovir disoproxil fumarate, with the highest score, is recommended as the first-line option, suitable for adults, children, and pregnant women. However, caution is warranted for potential renal impairment. Tenofovir alafenamide fumarate is recommended as a second-line alternative, particularly for individuals at high risk for bone and renal damage. Entecavir has a score similar to tenofovir alafenamide fumarate but requires dosing on an empty stomach and dose adjustment based on renal function of patients. Tenofovir amibufenamide received the lowest score and is considered a weak recommendation. The clinical application of these nucleoside (acid) analogues should be individualized based on the patient’s age, physiological status, and risk factors.
5.Palpitations, Shortness of Breath, Weakness in Limbs, Edema, and Dyspnea: A Rare Inflammatory Myopathy with Positive Aniti-mitochondrial Antibodies and Cardiac Involvement
Chunsu LIANG ; Xuchang ZHANG ; Ning ZHANG ; Lin KANG ; Xiaohong LIU ; Jiaqi YU ; Yingxian LIU ; Lin QIAO ; Yanli YANG ; Xiaoyi ZHAO ; Ruijie ZHAO ; Na NIU ; Xuelian YAN
Medical Journal of Peking Union Medical College Hospital 2025;16(1):248-255
This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.
6.DIA Proteomics Reveals Mechanism of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis Extract in Treating α-Syn Transgenic Parkinson's Disease in Mice
Qi ZHENG ; Yi LU ; Donghua YU ; Liangyou ZHAO ; Chunsheng LIN ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):40-50
ObjectiveTo investigate the mechanism of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis extract (ASH) in treating Parkinson's disease (PD) in mice by Data-Independent Acquisition (DIA) proteomics. MethodsThe α-Synuclein (α-Syn) transgenic PD mice were selected as suitable models for PD, and they were randomly assigned into PD, ASH (61.25 mg·kg-1), and Madopar (97.5 mg·kg-1) groups. Male C57BL/6 mice of the same age were selected as the control group, with eight mice in each group. Mice were administrated with corresponding drugs by gavage once a day for 20 days. The pole climbing time and the number of autonomic activities were recorded to evaluate the exercise ability of mice. Hematoxylin-eosin staining was employed to observe neuronal changes in the substantia nigra of PD mice. Immunohistochemistry (IHC) was employed to measure the tyrosine hydroxylase (TH) activity in the substantia nigra and assess the areal density of α-Syn in the striatum. DIA proteomics was used to compare protein expression in the substantia nigra between groups. IHC was utilized to validate key differentially expressed proteins, including Lactotransferrin, Notch2, Ndrg2, and TMEM 166. The cell counting kit-8 (CCK-8) method was used to investigate the effect of ASH on the viability of PD cells with overexpression of α-Syn. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the protein and mRNA levels of Lactotransferrin, Notch2, Ndrg2, and TMEM 166 in PD cells. ResultsCompared with the control group, the model group showed prolonged pole climbing time, diminished coordination ability, reduced autonomic activities (P<0.01), and reduced swelling neurons. Compared with the model group, ASH and Madopar reduced the climbing time, increased autonomic activities (P<0.01), and ameliorated neuronal damage. Compared with the control group, the model group showed a decrease in TH activity in the substantia nigra and an increase in α-Syn accumulation in the striatum (P<0.01). Compared with the model group, the ASH group showed an increase in TH activity and a reduction in α-Syn accumulation (P<0.05). DIA proteomics revealed a total of 464 differentially expressed proteins in the model group compared with the control group, with 323 proteins being up-regulated and 141 down-regulated. A total of 262 differentially expressed proteins were screened in the ASH group compared with the model group, including 85 proteins being up-regulated and 177 down-regulated. Kyoto encylopedia of genes and genomes (KEGG) pathway analysis indicated that ASH primarily regulated the Notch signaling pathway. The model group showed up-regulation in protein levels of Notch2, Ndrg2, and TMEM 166 and down-regulation in the protein level of Lactotransferrin compared with the control group (P<0.01). Compared with the model group, ASH down-regulated the protein levels of Notch2, Ndrg2, and TMEM 166 (P<0.05) while up-regulating the protein level of Lactotransferrin (P<0.01). The IHC results corroborated the proteomics findings. The cell experiment results showed that compared with the control group, the modeling up-regulated the mRNA and protein levels of Notch2, Ndrg2, and TMEM 166 (P<0.01), while down-regulating the mRNA and protein levels of Lactotransferrin (P<0.01). Compared with the model group, ASH reduced the mRNA and protein levels of Notch2, Ndrg2, and TMEM 166 (P<0.01), while increasing the mRNA and protein levels of Lactotransferrin (P<0.05, P<0.01). ConclusionASH may Synergistically inhibit the Notch signaling pathway and mitigate neuronal damage by down-regulating the expression of Notch2 and Ndrg2. Additionally, by up-regulating the expression of Lactotransferrin and down-regulating the expression of TMEM166, ASH can address brain iron accumulation, intervene in ferroptosis, inhibit mitophagy, and mitigate reactive oxygen species damage, thereby protecting nerve cells and contributing to the treatment of PD.
7.Efficacy of Fufang Lingjiao Jiangya Pills with Different Proportions of Goat Horn Replacing Antelope Horn on Spontaneous Hypertensive Rats
Tengjian WANG ; Wanlu ZHAO ; Yang YU ; Yan LIU ; Kun CAO ; Zheyuan LIN ; Yue WU ; Lilan LUO ; Weizhi LAI ; Zhaohuan LOU ; Qiaoyan ZHANG ; Quanlong ZHANG ; Luping QIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):68-78
ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats (SHR). In this experiment, 50 SHR rats were randomly grouped as follows: model (n=8), captopril (0.01 g·kg-1) (n=6), low-dose blank Fufang Lingjiao Jiangya pills (0.342 g·kg-1) (n=6), high-dose blank Fufang Lingjiao Jiangya pills (0.684 g·kg-1) (n=6), low-dose antelope horn-containing Fufang Lingjiao Jiangya pills (0.378 g·kg-1) (n=6), high-dose antelope horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1) (n=6), low-dose goat horn-containing Fufang Lingjiao Jiangya pills (0.378 g·kg-1) (n=6), and high-dose goat horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1) (n=6). Additionally, 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration, 3 h post administration, and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions, 48 SHR rats were randomly grouped as follows: model, blank Fufang Lingjiao Jiangya pills (0.684 g·kg-1), antelope horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1), 2× goat horn-containing Fufang Lingjiao Jiangya pills (0.824 g·kg-1), 4× goat horn Fufang Lingjiao Jiangya pills (0.969 g·kg-1), and 6× goat horn Fufang Lingjiao Jiangya pills (1.112 g·kg-1). The normal group included 8 WKY rats, and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks, and blood pressure was recorded at various time points (pre-administration, 3 h post administration, and on days 4, 7, 10, and 14 of administration). Serum levels of angiotensin-converting enzyme (ACE), angiotensin Ⅱ(Ang Ⅱ), renin, and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart, kidney, and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2, angiotensin Ⅱ type 1 receptor (AT1R), and angiotensinogen (AGT) in the kidney tissue were determined by Western blot, while the expression of nuclear factor (NF)-κB p65 and Toll-like receptor 4 (TLR4) in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group, all treatment groups showed lowered blood pressure (P<0.05, P<0.01), and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group, the model group showed elevated serum levels of ACE, Ang Ⅱ, renin, and IL-6, while the elevations were declined in the Fufang Lingjiao Jiangya pills groups (P<0.05, P<0.01). Pathological changes in the heart, kidney, and thoracic aorta were alleviated in all the treatment groups, with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R, AGT, NF-κB p65, and TLR4 and up-regulated protein levels of ACE2 (P<0.05, P<0.01) compared with model group, with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system (RAAS) and TLR4/NF-κB signaling pathways.
8.Status of Clinical Practice Guideline Information Platforms
Xueqin ZHANG ; Yun ZHAO ; Jie LIU ; Long GE ; Ying XING ; Simeng REN ; Yifei WANG ; Wenzheng ZHANG ; Di ZHANG ; Shihua WANG ; Yao SUN ; Min WU ; Lin FENG ; Tiancai WEN
Medical Journal of Peking Union Medical College Hospital 2025;16(2):462-471
Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.
9.Analysis of Mechanism of Astragaloside Ⅳ in Regulating Ferroptosis Through SLC7A11/GPX4 Pathway Against Vascular Smooth Muscle Cell Proliferation
Guoting LI ; Changchao YANG ; Lin LIU ; Weikang LI ; Zixian ZHAO ; Quan SHEN ; Jingshan ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):159-167
ObjectiveTo investigate the effect of astragaloside Ⅳ(AS-Ⅳ) on the proliferation of vascular smooth muscle cells(VSMCs) induced by angiotensin Ⅱ(Ang Ⅱ) based on solute carrier family 7 member 11/glutathione peroxidase 4(SLC7A11/GPX4) pathway. MethodsPrimary rat thoracic aortic VSMCs were cultured by tissue explant method, and the cell types were identified by immunofluorescence. Cell counting kit-8(CCK-8) was used to determine the optimal concentration and time of AS-Ⅳ after Ang Ⅱ stimulation. The experiment was divided into blank group, model group, AS-Ⅳ group(40 μmol·L-1), Erastin group(0.5 μmol·L-1), Erastin+AS-Ⅳ group(0.5 μmol·L-1+40 μmol·L-1). The blank group was cultured in normal medium, the model group was cultured in medium containing Ang Ⅱ(0.1 μmol·L-1), and each administration group was cultured in medium containing Ang Ⅱ(0.1 μmol·L-1) and the corresponding doses of drug. CCK-8 and plate clone formation assay were used to detect the proliferation of cells in each group, Prussian blue staining was used to detect cell iron deposition, the content of reactive oxygen species(ROS) in cells was detected by fluorescence probe method, the content of malondialdehyde(MDA) was detected by thiobarbituric acid(TBA) method, and the protein levels of SLC7A11 and GPX4 in each group were detected by Western blot. ResultsPrimary rat thoracic aortic VSMCs were successfully cultured by tissue explant method, and immunofluorescence detection showed that positive expression of α-smooth muscle actin(α-SMA) and negative expression of vimentin in the cells, identifying them as VSMCs. The optimal concentration and time of AS-Ⅳ determined by CCK-8 were 40 μmol·L-1 and 24 h, respectively. Pharmacodynamic studies showed that compared with the blank group, the cell proliferation in the model group increased, the iron deposition in the cells increased, the contents of ROS and MDA increased, and the expression levels of SLC7A11 and GPX4 proteins decreased(P<0.05, P<0.01). Compared with the model group, the cell proliferation of the AS-Ⅳ group was inhibited, the iron deposition in the cells was decreased, the contents of ROS and MDA were decreased, and the expression levels of SLC7A11 and GPX4 proteins were increased(P<0.05, P<0.01). While in the Erastin group, the cell proliferation was increased, the iron deposition was increased, ROS and MDA contents were increased, and the expression levels of SLC7A11 and GPX4 proteins were decreased(P<0.05, P<0.01). Compared with the AS-Ⅳ group, Erastin+AS-Ⅳ group showed increased cell proliferation, increased iron deposition in cells, increased ROS and MDA contents, and decreased expression of SLC7A11 and GPX4 proteins(P<0.05). Compared with the Erastin group, the cell proliferation in Erastin+AS-Ⅳ group was inhibited, the iron deposition was decreased, the contents of ROS and MDA were decreased, and the expression levels of SLC7A11 and GPX4 proteins were increased(P<0.05, P<0.01). ConclusionAS-Ⅳ can inhibit ferroptosis by regulating the SLC7A11/GPX4 pathway, so as to weaken the proliferation of VSMCs, thus playing a role in the treatment of atherosclerosis.
10.Association between negative life events and smartphone addiction among middle school students
Chinese Journal of School Health 2025;46(5):619-623
Objective:
To explore the association between negative life events and smartphone addiction among middle school students, so as to provide theoretical support and practical guidance for prevention and intervention of smartphone addiction among middle school students.
Methods:
Using cluster sampling, 8 890 students were selected to survey from 27 junior high schools and 3 senior high schools in a district of Shenzhen in 2022 (baseline) and 2023 (followup). Data were collected through selfresigned questionnaires on basic information, the Smartphone Addiction Scale-Short Version, and the Adolescent Selfrating Life Events Checklist. Mixedeffects models were employed to analyze the association.
Results:
Compared to 2022, the punishment scores of middle school students in 2023 [1.00 (0.00, 6.00) and 1.00 (0.00, 6.00)] decreased (Z=4.27), while the scores of interpersonal stress, learning stress and adaptation [4.00(0.00, 8.00), 4.00(0.00, 8.00); 4.00(1.00, 8.00), 5.00(2.00, 9.00); 2.00 (0.00, 6.00), 3.00 (0.00, 7.00)] increased (Z=-3.04, -8.36, -6.80) (P<0.01). Mixedeffects models revealed a positive doseresponse relationship between negative life events and smartphone addiction (OR=1.08-1.17, P<0.01). Stepwise regression showed independent positive effects of interpersonal stress (OR=1.05), academic stress (OR=1.03), and adaptation stress (OR=1.11) on smartphone addiction (P<0.01). Subgroup analysis of nonaddicted students in 2022 confirmed persistent associations for academic stress (OR=1.03) and adaptation (OR=1.07) (P<0.01).
Conclusion
Negative life events exhibit a positive doseresponse relationship with smartphone addiction, particularly interpersonal stress, academic stress, and adaptationrelated events.


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