ObjectiveTo investigate the epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer by regulating DNA methylation， and to provide a basis for scientific clinical medication. MethodsA total of 48 specific pathogen-free Sprague-Dawley rats were divided into normal group， model group， and Diwu Yanggan Capsule group using a random number table， with 16 rats in each group. The Solt-Farber two-step method was used to establish a rat model of liver cancer. The rats in the Diwu Yanggan Capsule group were given Diwu Yanggan Capsule at a dose of 750 mg/kg/d by gavage， and those in the normal group and the model group were given an equal volume of normal saline by gavage. Liver tissue samples were collected from each group of rats after 16 weeks of continuous intervention； DNA methylation chips were used to analyze the change in DNA methylation in liver tissue， and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were used for data analysis. In addition， the MeDIP-PCR technique was used to detect the changes in candidate differentially methylated genes such as YWHAB， ADCK2， ERLIN2， SEMA3B， and TPH2 in the liver tissue of rats， and Western blot and RT-qPCR were used to verify the expression of key methylated genes. The independent-samples t test was used for comparison of continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups， while the least significant difference t-test was used for further comparison between two groups. ResultsThe DNA methylation chip analysis showed that compared with the normal group， the model group had significant methylation changes in the promoter region of 2 422 genes in liver tissue of rats. The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed that these differentially methylated genes were significantly enriched in metabolic pathways such as steroid hormone biosynthesis and drug metabolism-cytochrome P450. Compared with the model group， the Diwu Yanggan Capsule group had significant reversal of promoter methylation in 1 650 genes， and the KEGG enrichment analysis showed that these genes were mainly involved in the pathways closely associated with cell proliferation， apoptosis， and microenvironment regulation， such as the calcium ion signaling pathway， the cAMP signaling pathway， and the extracellular factor signaling pathway. Compared with the model group， the Diwu Yanggan Capsule group had a significant increase in the promoter methylation level of the ADCK2 gene （P<0.05） and significant reductions in the promoter methylation levels of the ERLIN2 and TPH2 genes （all P<0.05）. Compared with the model group， the Diwu Yanggan Capsule group had significant reductions in the mRNA expression levels and the protein expression levels of the ADCK2 （all P<0.05）. ConclusionAbnormal DNA methylation in liver tissue participates in the development and progression of liver cancer. The effect of Diwu Yanggan Capsule on DNA methylation level is an important epigenetic mechanism for its effect in the prevention and treatment of liver cancer.

OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

Objective: To observe the clinical efficacy and safety of Yiqi Tongluo Decoction in the intervention of early traditional Chinese medicine (TCM) syndromes after ischemic cerebrovascular disease (ICVD) intervention. Methods: From October 2020 to July 2023, a randomized, double-blind, placebo-controlled study was conducted to include 60 patients with qi deficiency, blood stasis, and phlegm obstruction syndrome after ICVD interventional therapy. They were assigned to the Yiqi Tongluo Decoction treatment group (30 cases) and the TCM placebo routine treatment control group (30 cases) according to the randomized block design. Both groups received routine standardized treatment of Western medicine, including dual antiplatelet, lipid regulation, and control of risk factors for cerebrovascular disease. The treatment group was treated with Yiqi Tongluo Decoction based on the control group. The course of treatment was 60 days and follow-up was carried out 2 and 6 months after the operation. The improvement of qi deficiency syndrome, blood stasis syndrome, phlegm syndrome score and TCM syndrome score, modified Rankin score (mRS), Barthel index (BI) score, Fatty acid-binding protein 4 (FABP4) level, incidence of transient ischemic attack (TIA) and ischemic stroke (IS) and incidence of adverse reactions, Head and neck CT angiography (CTA) or digital subtraction angiography (DSA) examination were collected. The clinical efficacy of the patients 2 months after the operation was taken as the main outcome index to preliminarily evaluate the early and long-term efficacy of Yiqi Tongluo Decoction after the ICVD intervention. The early and long-term clinical efficacy and safety of Western medicine standardized treatment combined with TCM Yiqi Tongluo Decoction on patients with qi deficiency, blood stasis and phlegm obstruction syndrome after ICVD intervention were evaluated. The safety of Yiqi Tongluo Decoction in the treatment of patients after ICVD intervention with white blood cell (WBC), C-reactive protein (CRP), fibrinogen (FIB), plasminogen time (PT), recurrence of cerebral ischaemia and restenosis in patients at 2 and 6 months after treatment were evaluated. Results: Compared to the control group, the TCM syndrome scores for qi deficiency, blood stasis and phlegm syndrome in the treatment group reduced significantly, the clinical efficacy improved significantly, the mRS score and FABP4 were reduced, and the BI score was increased. Adverse events such as cerebral ischaemia were fewer in the treatment group than in the control group, but the difference was not statistically significant; levels of CRP, WBC and PT were reduced, and levels of FIB were reduced at 6 months post-treatment, all P<0.01, and images were intuitively compared. The treatment group was superior to the control group. Conclusion Yiqi Tongluo Decoction combined with Western medicine standard treatment can improve the early clinical efficacy of ICVD patients with qi deficiency, blood stasis and phlegm obstruction syndrome after interventional surgery, improve neurological impairment and daily living ability, reduce the state of qi deficiency syndrome, blood stasis syndrome and phlegm syndrome after interventional surgery, and improve the clinical efficacy of TCM. At the same time, it can reduce the level of FABP4, the target of atherosclerosis and restenosis after interventional surgery, reduce the level of inflammation after interventional surgery in patients with ICVD, regulate coagulation function, and reduce the incidence of long-term recurrence of cerebral ischemia after interventional surgery, with good safety.

Objective: To investigate the changing trends for associations of anxiety and depressive symptoms with smartphone addiction among middle school students, so as to provide a scientific basis for preventing smartphone addiction in middle school students. Methods: From 2022 to 2023, a method of combining convenient sampling with cluster sampling was used to select 8 923 middle school students from 27 junior high schools and 3 senior high schools in a district of Shenzhen City between September 2022 (baseline, T1) and September 2023 (follow up, T2). The Smartphone Addiction Scale-Short Version (SAS-SV), Patients Health Questionnaire-9 Item (PHQ-9), and Generalized Anxiety Disorder 7-item Scale (GAD-7) were administered to assess smartphone addiction, anxiety and depressive symptoms. Mixed effects models were used to analyze the association of anxiety and depressive symptoms with smartphone addiction among middle school students. Results: From September 2022 to September 2023, the reported prevalence of smartphone addiction increased from 24.22% to 25.25% ( χ 2=45.71); and smartphone addiction scores [ 24.00 (16.00, 32.00),25.00(16.00, 33.00)], anxiety symptom scores [2.00(0.00, 7.00),3.00(0.00, 7.00)] and depressive symptom scores[3.00(0.00, 8.00),5.00(0.00, 9.00)] all significantly increased ( Z =-17.43, -42.38, -41.57) (all P <0.05). There were statistically significant difference in the distribution of anxiety and depression symptom levels among middle school students in 2022 and 2023 ( χ 2=85.15, 106.85, both P <0.05). After adjusting for covariates such as age, gender and family background, mixed effects models revealed dose response associations of anxiety and depressive symptoms with smartphone addiction among middle school students:mild anxiety symptom( OR =3.22), moderate to severe anxiety symptom ( OR =5.36), mild depressive symptom ( OR =3.32) and moderate to severe depressive symptom ( OR =6.13) were significantly associated with higher risks of smartphone addiction (all P <0.05). Interaction effect analysis found that co existing anxiety and depressive symptoms synergistically increased addiction risk by 5.60 times ( OR =5.60) compared to the asymptomatic group, with 32% of the combined risk attributable to their interaction ( S=1.64, AP =0.32)(both P < 0.05 ). Conclusions Anxiety and depressive symptoms are significantly associated with smartphone addiction, exhibiting a synergistic effect. Attention should be paid to emotional issues and smartphone addiction among middle school students.

OBJECTIVE: To explore the pain-location interaction between pressure-sensitive points on the body surface and traditional acupoints in patients with chronic non-specific low back pain (CNLBP) under different disease courses, using Euclidean distance and multivariate statistical analysis. METHODS: A pressure-sensitive point detection was performed on 30 CNLBP patients with varying disease courses. A constant pressure was applied using an FDK20 algometer within a designated lumbar area, a total of 50 points were tested, and the tested points were numbered; the visual analogue scale (VAS) pain score was recorded simultaneously. MatlabR2022a9.12. software was used to extract the positions of pressure-sensitive points, and preprocessing and normalization of point location and VAS scores data were conducted. Under constraint conditions (VAS≥8.0 ∩ Euclidean distance to acupoint≤0.5), the proportion of pressure-sensitive points within the Euclidean distance threshold to each acupoint (PVD_acupoint) was calculated, followed by multivariate statistical analysis. RESULTS: ①Constrained analysis of PVD_acupoint showed that PVD_{Qihaishu (BL24)} and PVD_{Dachangshu (BL25)} were positively correlated with disease course (r=0.55, P<0.01). ②Factor analysis and silhouette analysis revealed that PVD_{Shenshu (BL23)} and PVD_{Dachangshu (BL25)} exhibited trends consistent with disease course progression (P>0.05), with different degree (P<0.01). CONCLUSION The PVD_acupoint value based on Euclidean distance can characterize the pressure sensitivity features of traditional acupoints associated with disease. Multivariate statistical analysis of PVD_acupoint confirms that selecting the acupoint combination of Shenshu (BL23) and Dachangshu (BL25) for CNLBP is associated with the distribution of surrounding pressure-sensitive points and the pathological characteristics of the condition.
Humans ; Acupuncture Points ; Low Back Pain/physiopathology* ; Male ; Female ; Middle Aged ; Adult ; Aged ; Acupuncture Therapy ; Young Adult ; Pressure

Objective:To apply artificial intelligence（AI）in classifying ovarian tumors on ultrasound images，and compare the diagnostic results of several sonographers with varying seniority levels.Methods:A total of 645 patients diagnosed with adnexal masses via gynecological ultrasound examination at Qilu Hospital of Shandong University from January 2021 to December 2024 were enrolled. Three deep learning architectures，i.e.，Alexnet，Densenet121，and Resnet50 were developed and used to internally test the classification effectiveness of ovarian tumors，while the optimal model was selected for external testing. Two junior sonographers and two senior sonographers were recruited to independently diagnose ovarian tumors in the external test dataset. Subsequently，the benign and malignant results of the model's predictions were disclosed to each sonographer，and their revised diagnoses on the same external test data in combination with the best AI model were recorded.Results:The optimal model achieved an accuracy of 0.941，sensitivity of 0.936，and specificity of 0.944 on the internal test dataset，and maintained robust performance on the external test dataset with accuracy of 0.891，sensitivity of 0.880，and specificity of 0.907. Compared to junior sonographers，the optimal model demonstrated significantly higher sensitivity in discriminating benign from malignant ovarian tumors（0.880 vs. 0.723，0.602；all P<0.05）. No statistically significant difference was observed in diagnostic accuracy between the optimal model and senior sonographer 1（ P=0.05）. With assistance from the optimal model，junior sonographers achieved significant improvements in both sensitivity and specificity（sensitivity：0.723 vs. 0.843，0.602 vs. 0.819；specificity：0.778 vs. 0.833，0.685 vs. 0.741；all P<0.05）. Conclusions:The optimal model achieves comparable performance to that of senior sonographers in ovarian tumor classification. With model assistance，the diagnostic performance of junior sonographers is significantly improved.

Objective:To explore the effect of exercise on the memory of rats modeling vascular cognitive impairment (VCI) and also its effects on the hippocampal Sema3G/neuropilin-2 (Nrp2)/PlexinA4 signaling pathway.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and an exercise group, each of 6. The model and exercise groups underwent VCI modeling via bilateral common carotid artery occlusion, while the sham-operated group received the same surgical procedure without vessel ligation or transection. Beginning forty-eight hours after the surgery, the exercise group carried out daily 30-minute treadmill training sessions, 5 days a week, for a total of 4 weeks, while the other two groups were placed on the same treadmill with it not in operation. After the intervention, cognitive functioning was assessed using the novel object recognition (NOR) test and a Y-maze test. Western blotting was employed to evaluate the expression of Sema3G, Nrp2, PlexinA4, and Rac1 in the hippocampus. Immunofluorescence staining was used to observe the distribution of Nrp2 and PlexinA4 in the hippocampus.Results:Compared with the model group, the exercise group exhibited significantly higher NOR indices during both the short-term and long-term memory testing phases after the intervention. Those rats also tended to have significantly longer total exploration times in the novel arm of the Y-maze test. The western blotting revealed that the expression levels of Sema3G, PlexinA4, and Rac1 in the hippocampus were significantly higher in the exercise group compared to the model group, on average. Immunofluorescence showed significantly increased PlexinA4 fluorescence intensity in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, and significantly elevated Nrp2 fluorescence intensity in the CA3 region in the exercise group compared to the model group. The Pearson correlation coefficients for Nrp2/PlexinA4 co-localization in the CA1, CA3 and DG regions were significantly higher in the exercise group than in the model group.Conclusions:Exercise training significantly improves memory function in rats with VCI, and this effect may be associated with activation of the hippocampal Sema3G/Nrp2/PlexinA4 signaling pathway.

Acquired dermal macular hyperpigmentation (ADMH) is a group of diseases clinically characterized by grayish-black macules and patches, with pigment predominantly deposited in the dermis. ADMH includes Riehl's melanosis, lichen planus pigmentosus, and erythema dyschromicum perstans/ashy dermatosis. In light of the remarkable similarities in both morphological and histopathological characteristics among this group of diseases, the academic community has recently proposed the new nosological term "acquired dermal macular hyperpigmentation" to achieve integration and unified classification of these related disorders. This review comprehensively elaborates on advances in the diagnosis and treatment of ADMH, including clinical manifestations, dermoscopic findings, pathological characteristics, and treatment progress.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.