1.Research progress on the mechanism of metformin in the intervention of cognitive impairment-related diseases
Yuan LIU ; Yumin XU ; Shiyu LIU ; Huayu YAN ; Xin YANG ; Hongcai XU ; Yabo WU
China Pharmacy 2025;36(15):1942-1946
Cognitive impairment (CI) is a clinical syndrome characterized by progressive decline in advanced cognitive functions such as memory, thinking, and judgment. Its etiology and pathogenesis are complex, and there is currently a lack of specific drug interventions. Metformin, as a first-line hypoglycemic drug for type 2 diabetes, not only lowers blood glucose levels but also improves CI. This article reviews and summarizes the pharmacological effects and mechanisms of metformin in improving Alzheimer’s disease, diabetes cognitive impairment, cognitive impairment after chemotherapy, in order to provide novel insights and approaches for the treatment of CI-related diseases. Studies have shown that the mechanism by which MET intervenes in CI mainly includes regulating β-amyloid protein and tau protein metabolism, reducing insulin resistance, inhibiting neuroinflammation, improving synaptic plasticity, improving mitochondrial dysfunction, regulating gut microbiota and lipid metabolism, etc. Future research needs to be conducted through interdisciplinary collaboration, fully integrating multiple omics data, and combining advanced technologies to further reveal their mechanisms of effect.
2.Introduction to Implementation Science Theories, Models, and Frameworks
Lixin SUN ; Enying GONG ; Yishu LIU ; Dan WU ; Chunyuan LI ; Shiyu LU ; Maoyi TIAN ; Qian LONG ; Dong XU ; Lijing YAN
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1332-1343
Implementation Science is an interdisciplinary field dedicated to systematically studying how to effectively translate evidence-based research findings into practical application and implementation. In the health-related context, it focuses on enhancing the efficiency and quality of healthcare services, thereby facilitating the transition from scientific evidence to real-world practice. This article elaborates on Theories, Models, and Frameworks (TMF) within health-related Implementation Science, clarifying their basic concepts and classifications, and discussing their roles in guiding implementation processes. Furthermore, it reviews and prospects current research from three aspects: the constituent elements of TMF, their practical applications, and future directions. Five representative frameworks are emphasized, including the Consolidated Framework for Implementation Research (CFIR), the Practical Robust Implementation and Sustainability Model (PRISM), the Exploration, Preparation, Implementation, Sustainment (EPIS)framework, the Behavior Change Wheel (BCW), and the Normalization Process Theory (NPT). Additionally, resources such as the Dissemination & Implementation Models Webtool and the T-CaST tool are introduced to assist researchers in selecting appropriate TMFs based on project-specific needs.
4.Ferrum@albumin assembled nanoclusters inhibit NF-κB signaling pathway for NIR enhanced acute lung injury immunotherapy.
Xiaoxuan GUAN ; Binbin ZOU ; Weiqian JIN ; Yan LIU ; Yongfeng LAN ; Jing QIAN ; Juan LUO ; Yanjun LEI ; Xuzhi LIANG ; Shiyu ZHANG ; Yuting XIAO ; Yan LONG ; Chen QIAN ; Chaoyu HUANG ; Weili TIAN ; Jiahao HUANG ; Yongrong LAI ; Ming GAO ; Lin LIAO
Acta Pharmaceutica Sinica B 2025;15(11):5891-5907
Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe3O4 loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4+/CD8+ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.
5.Research progress on the pharmacological mechanisms of Acorus tatarinowii-Polygala tenuifolia herb pair in ameliorating cognitive impairment
Xin YANG ; Yumin XU ; Huayu YAN ; Yuan LIU ; Shiyu LIU ; Hongcai XU ; Yabo WU
China Pharmacy 2025;36(23):3007-3011
Cognitive impairment is a major public health challenge facing global aging societies, and currently lacks effective treatment measures. Herb pair, characterized by their rigorous compatibility and synergistic effects, demonstrate unique advantages in clinical practice. Acorus tatarinowii-Polygala tenuifolia is a classic herbal pair for treating cognitive impairment, widely utilized in various traditional Chinese medicine formulations, such as Kaixin san, Shenghui tang, and Yuanzhi san. This article summarizes the pharmacological mechanisms of A. tatarinowii, P. tenuifolia and their compatible compound prescriptions in ameliorating cognitive impairment. It is found that they can exert effects in ameliorating cognitive impairment through mechanisms such as reducing amyloid β-protein deposition and inhibiting excessive phosphorylation of Tau protein, suppressing inflammatory responses, alleviating oxidative stress, protecting neurons and regulating neurotransmitters, modulating the structure and function of the blood- brain barrier, and regulating autophagy. Subsequently, in-depth analysis can be conducted on the active ingredients of A. tatarinowii- P. tenuifolia herb pair that ameliorate cognitive impairment, along with the addition of relevant clinical trials for verification. This will provide theoretical foundations and research approaches for the treatment of cognitive impairment using traditional Chinese medicine.
6.Diagnostic value of serum serine protease Corin in patients with chronic renal failure complicated with heart failure
Pengfei ZHOU ; Shiyu LIU ; Wen FANG ; Ruihua CHEN ; Zihan ZHOU ; Xiaomei HOU ; Yutong YAN ; Yahui HU
Chinese Journal of Laboratory Medicine 2024;47(6):610-618
Objective:To investigate the diagnostic value of serum serine protease (Corin) in chronic renal failure (CRF) complicated with heart failure.Methods:A retrospective analysis was conducted on 120 patients, (64.05±13.89) years old, 77 male (64.17%), with chronic renal failure combined with heart failure admitted to Zhengzhou People′s Hospital from January 1, 2023, to December 31, 2023. The control group consisted of 87 patients, (60.59±8.78) years old, 54 male (62.07%), with simple chronic renal failure. Clinical information, laboratory test indicators and echocardiographic parameters were collected. Serum Corin concentration was measured using enzyme-linked immunosorbent assay (ELISA). The experimental group was divided into grade Ⅱ(31 cases), grade Ⅲ(47 cases) and grade Ⅳ(42 cases) according to the New York College of Cardiology heart function classification system. Serum Corin levels were compared between the experimental group and the control group and among different cardiac function grades. Spearman correlation analysis was performed to evaluate the relationship between serum Corin and brain natriuretic peptide (BNP), D-dimer. ROC analysis was conducted to assess the predictive value of serum Corin in CRF complicated with heart failure and cardiac function classification; Binary Logistic regression was used to construct a multi-index joint prediction model, the joint prediction probability was obtained, and ROC curve was drawn to compare the diagnostic value of serum Corin and BNP in CRF combined with heart failure and the diagnostic value of serum Corin combined with D-dimer and BNP in CRF combined with heart failure.Results:The serum Corin level[2 568.97±477.70 pg/ml vs. 1 727.81±480.60 pg/ml, t=12.47, P<0.001], BNP [700.00(256.00, 2 089.75) pg/ml compared with 88.00 (43.00, 230.00) pg/ml, Z=-9.00, P<0.001], D-dimer [1 150.00(643.00, 1 874.75)μg/L compared with 556.00 (301.00, 865.00)μg/L, Z=-6.57, P<0.001] in chronic renal failure complicated with heart failure group was higher than that in simple CRF group, and the difference was statistically significant. Among patients with CRF complicated with heart failure, serum Corin[2 231.74±311.39 pg/ml vs. 2 562.09±365.30 pg/ml vs. 2 825.57±536.83 pg/ml, F=74.33, P<0.001], BNP [234.00(168.00, 612.00) pg/ml compared with 514.00(260.00, 1 455.00) pg/ml compared with 2 200.00(640.50, 4 682.75) pg/ml, H=29.42, P<0.001], D-dimer [753.00(514.00, 1 280.00) μg/L compared with 1 187.00(590.00, 1 840.00) μg/L compared with 1 603.00(810.00, 3 313.25) μg/L, H=14.98, P<0.001] increased with the increase of cardiac function grade, and the difference was statistically significant. According to Spearman correlation analysis, serum Corin was positively correlated with BNP ( r=0.409) and D-dimer ( r=0.299), P<0.001. According to the ROC analysis, the AUC of serum Corin in the diagnosis of CRF complicated with heart failure and cardiac function grade Ⅱ, Ⅲ, Ⅳ were 0.890(95% CI 0.846-0.935), 0.807 (95% CI 0.728-0.885), 0.911 (95% CI 0.864-0.959), 0.927 (95% CI 0.882-0.972) respectively; the AUC of BNP in the diagnosis of CRF complicated with heart failure was 0.867 (95% CI 0.817-0.916), the AUC of serum Corin combined with D-dimer, BNP combined with D-dimer, serum Corin combined with D-dimer and BNP in the diagnosis of CRF complicated with heart failure were respectively 0.930 (95% CI 0.897-0.962), 0.892 (95% CI 0.847-0.936), 0.952 (95% CI 0.927-0.977). Conclusions:Serum Corin expression is elevated in patients with CRF complicated with heart failure, and the degree of elevation is related to cardiac function grade. Serum Corin has a good diagnostic value for CRF complicated with heart failure and its severity. Serum Corin is expected to become a new biomarker for diagnosis of CRF complicated with heart failure.
7.A single center study of influence on the prognosis of children with septic shock in PICU
Qing CHEN ; Jianli CHEN ; Ping LING ; Rong TANG ; Shiyu LUO ; Yan LUO ; Xuexin WANG ; Yi LIN ; Sha WANG
Chinese Pediatric Emergency Medicine 2024;31(11):856-860
Objective:To analyze the prognostic factors of children with septic shock in the pediatric intensive care unit.Methods:The clinical data of children diagnosed with septic shock in the pediatric intensive care unit of Guiyang Maternal and Child Health Hospital from April 2018 to April 2022 were retrospectively collected,and the children were divided into the death group and the survival group according to seven days regression.The basic data of the two groups were statistically compared,and the relationship between lactic acid,vasoactive-inotropic score one hour after admission,time of antibiotic initiation,serum potassium,serum sodium,serum calcium,serum troponin T,fluid resuscitation volume in the first hour,glutamyl aminotransferase,creatinine,total leukocyte count,C-reaction protein,brain natriuretic peptide were compared.The risk factors affecting the death of children were analyzed by Logistic regression.The relationship between fluid resuscitation volume in the first hour and prognosis was analyzed using the receiver operator characteristic (ROC) curve.Results:(1)A total of 67 children were included,19 died and 48 survived.(2)The first-hour liquid resuscitation dose in the survival group was lower than that in the death group,and the difference was statistically significant( P<0.05).(3)The ROC curve showed that the optimal cut-off of the first-hour liquid resuscitation dose was 25 mL/kg,with a sensitivity of 57.9% and a specificity of 72.9%.(4)In unifactorial analysis,lactic acid in the first hour of admission,early lactic acid after resuscitation,serum calcium,serum troponin T,alanine aminotransferase,combined septic encephalopathy,Glasgow coma score,and pediatric critical illness score were all risk factors for death in children within seven days( P<0.05).(5) Multivariate Logistic regression analysis showed that serum calcium( OR=1.435, P=0.001)and lactic acid value after resuscitation( OR=0.040, P=0.021)were independent risk factors for death in septic shock. Conclusion:The higher the total fluid resuscitation in the first hour,the higher the fatality rate.Serum calcium and early lactic acid after resuscitation are independent risk factors for death in children within seven days.
8.Haploidentical donor peripheral blood stem cell transplantation using third-party cord blood compared with matched unrelated donor transplantation for patients with hematologic malignancies
Xia MA ; Yan CHEN ; Yi LIU ; Tingting CHENG ; Xu CHEN ; Cong ZENG ; Juan HUA ; Shiyu WANG ; Yjing XU
Chinese Journal of Hematology 2024;45(2):141-147
Objectives:To assess the efficacy of cord blood-assisted haploid peripheral blood stem cell transplantation (haplo-cord-PBSCT) versus unrelated donor peripheral blood stem cell transplantation (UD-PBSCT) in the treatment of malignant hematological diseases.Methods:A retrospective analysis was performed on one hundred and four patients with malignant hematological diseases who underwent haplo-cord-PBSCT and fifty-two patients who underwent UD-PBSCT at Xiangya Hospital of Central South University between January 2016 and December 2021.Results:①The median implantation time for neutrophils in the haplo-cord-PBSCT and UD-PBSCT groups was 13 (9–22) days and 13 (10–24) days, respectively ( P=0.834), whereas the median implantation time for platelets was 15 (7–103) days and 14 (8-38) days, respectively ( P=0.816). The cumulative implantation rate of neutrophils at 30 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group was 100% ( P=0.314), and the cumulative platelet implantation rate at 100 days after transplantation was 95.2% (95% CI 88.3% - 98.1% ) and 100% ( P=0.927), respectively. 30 days after transplantation, both groups of patients achieved complete donor chimerism, and no umbilical cord blood stem cells were implanted. ②The cumulative incidence rates of grade Ⅱ-Ⅳ acute GVHD within 100 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group were 29.1% (95% CI 20.1% –38.1% ) and 28.8% (95% CI 17.2% –41.6% ( P=0.965), respectively. The cumulative incidence rates of grade Ⅲ/Ⅳ acute GVHD were 7.8% (95% CI 3.6% –14.0% ) and 9.6% (95% CI 3.5% –19.5% ) ( P=0.725). The cumulative incidence rates of 2-year chronic GVHD in the haplo-cord-PBSCT group and the UD-PBSCT group were 45.3% (95% CI 36.1% -56.1% ) and 35.1% (95% CI 21.6% –44.1% ), respectively ( P=0.237). The cumulative incidence rates of severe chronic GVHD at 2 years after transplantation were 13.6% (95% CI 7.6% -21.3% ) and 12.9% (95% CI 5.1% -24.3% ), respectively ( P=0.840). ③The 2-year CIR after transplantation in the haplo-cord-PBSCT group and UD-PBSCT group were 12.8% (95% CI 7.0% –20.5% ) and 10.0% (95% CI 3.6% –20.2% ), respectively ( P=0.341), and the NRM were 14.7% (95% CI 8.4% –22.6% ) and 16.2% (95% CI 7.4% –28.0% ), respectively ( P=0.681). ④The 2-year OS rates in the haplo-cord-PBSCT and UD-PBSCT groups after transplantation were 82.2% (95% CI 74.8% –90.3% ) and 75.5% (95% CI 64.2% -88.7% ), respectively ( P=0.276). The 2-year DFS rates were 69.9% (95% CI 61.2% –79.8% ) and 73.8% (95% CI 62.4% -87.3% ), respectively ( P=0.551). The 2-year rates of GVHD-free/recurrence-free survival (GRFS) were 55.3% (95% CI 44.8% -64.8% ) and 64.7% (95% CI 52.8% –79.3% ), respectively ( P=0.284) . Conclusion:The findings of this study indicate that haplo-cord-PBSCT and UD-PBSCT have comparable efficacy and safety in the treatment of malignant hematological diseases and can be used as an alternative treatment options.
9.Evaluation of the efficacy and safety of ultrasound-guided pulsed radiofrequency treatment for knee osteoarthritis in patients with cardiovascular disease
Dandan ZHANG ; Suoliang WANG ; Huiyong NIE ; Yanping REN ; Shiyu WANG ; Shaoyao YAN
Journal of Chinese Physician 2024;26(9):1313-1317
Objective:To comprehensively evaluate the clinical efficacy and safety of pulse radiofrequency therapy for knee osteoarthritis (KOA) with cardiovascular disease (CVD).Methods:A total of 132 patients with knee osteoarthritis (KOA) and cardiovascular disease (CVD) admitted to the First Affiliated Hospital of Xi′an Jiaotong University from March 2022 to February 2024 were randomly divided into two groups using a random number table method. Group A (65 cases) received ultrasound-guided pulse radiofrequency treatment of the hidden nerve, while group B (67 cases) received oral etoposide tablets and intra-articular injection of sodium hyaluronate. Basic data such as age, gender, height, weight, body mass index (BMI), knee joint function grading (K-L grading), and distribution of cardiovascular disease types were recorded between the two groups. The degree of knee joint pain [Visual Analog Scale (VAS) score] and Knee Joint Function Score (OKS), Athens Insomnia Scale (AIS) scores and incidence of complications. were compared between the two groups at 1 week, 1 month, 3 months, and 6 months after treatment.Results:The VAS score of group A showed a slow decreasing trend from 1 week to 6 months after treatment. The VAS score of group B decreased to the lowest level one week after treatment and gradually increased within 6 months after treatment. The VAS scores of both groups improved after 1 week of treatment and at 1, 3, and 6 months of treatment compared to preoperative levels ( F=703.955, P<0.001), and the degree of postoperative pain improvement in the group A was better than that in the group B ( F=106.575, P<0.001). The OKS of both groups decreased significantly after 1 week of treatment and at 1, 3, and 6 months of treatment, and the time effect was statistically significant ( F=2 233.447, P<0.001). The OKS of the group A was lower than that of group B after 1 week of treatment and at 1, 3, and 6 months of treatment, and the difference was statistically significant ( F=141.214, P<0.001). The AIS scores improved significantly after 6 months of treatment compared to preoperative levels ( F=1 044.424, P<0.001), and the group A had better AIS scores than the group B at 1, 3, and 6 months of treatment, with statistically significant differences ( F=124.864, P<0.001). There was no statistically significant difference in postoperative complications between the two groups ( P>0.05). Conclusions:Ultrasound guided pulsed radiofrequency treatment of KOA with CVD can significantly alleviate postoperative pain, improve joint mobility and sleep quality, and is more effective than traditional conservative treatment of oral etoposide tablets combined with intra-articular injection of sodium hyaluronate.
10.Dosimetric analysis of CBCT imaging frequency and matching strategy in prostate cancer radiotherapy
Yan GAO ; Xianshu GAO ; Mingwei MA ; Xueying REN ; Jiayan CHEN ; Lin MA ; Lei HUANG ; Shiyu SHANG
Chinese Journal of Radiation Oncology 2024;33(8):733-739
Objective:To evaluate the effects of different imaging frequencies and matching strategies of cone-beam computed tomography (CBCT) on dose-volume parameters in target and organs at risk (OAR) during image-guided radiotherapy for prostate cancer.Methods:A total of 561 sets of CBCT images from 21 patients treated with radical prostate radiotherapy who were admitted to Peking University First Hospital from June 2022 to May 2023 were retrospectively analyzed. All patients received volumetric intensity modulated arc therapy (VMAT) at a prescribed dose of 70 Gy divided into 25 times, 2.8 Gy per time. Clinical target volume (CTV) and OAR were delineated by the same oncologist on each CBCT image. The planned CT (pCT) was rigorously registered to CBCT after calibration of positioning errors according to different image guidance modes and frequencies, and CT values and structures were propagated to CBCT through deformable image registration (DIR). The daily dose was mapped to pCT according to the deformation vector field (DVF) for dose accumulation. The actual cumulative dose of daily online CBCT validation was compared with the weekly CBCT validation regimen (days 1, 2, 3, 6, 11, 16 and 21 online imaging). The dosimetric comparison was also made between bone-based matching and soft tissue-based matching (after automatic bone-based matching, manual prostate-based matching was performed and fine-tuning was made regarding the anterior wall of rectum). Wilcoxon signed rank-sum test was utilized to analyze dose-volume parameters between planned and cumulative doses that exhibited non-normal distribution, while paired t-test was employed for assessing shift values and average dose parameters that demonstrated normal distribution. Results:Compared with daily CBCT image guidance, the CTV_D 98% in weekly CBCT was significantly reduced [(69.08±1.58) vs. (65.24±3.64) Gy, P<0.001]. The CTV_D 98% of bone-based matching was (69.27±2.14) Gy, but the high-dose volume of the rectum were significantly increased: V 60 Gy was 3.18%±3.10%, V 65 Gy was 0.77%±1.23%. The target area coverage using soft tissue-based matching is sufficient, with a CTV_D 98% of (69.08±1.58) Gy. And the percentage volume of high-dose volume of the rectum was significantly reduced, with V 60 Gy being 2.02%±2.42% and V 65 Gy being 0.34%±0.68%. Conclusions:In prostate cancer patients undergoing moderately-fractionated radiotherapy, daily CBCT image guidance demonstrates superior target coverage compared to a weekly scheme. Soft tissue-based matching, which is automatic bone-based matching followed by manual soft tissue-based matching and fine-tuning according to the anterior rectal wall, offers better rectal protection while maintaining target coverage.

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