1.Mechanism of Mingshi Prescription in Regulating Opn4-dopamine Axis to Inhibit Endoplasmic Reticulum Stress and Delay Myopia Progression
Baohua LI ; Zefeng KANG ; Lulu WANG ; Xin YAN ; Jianquan WANG ; Xinyue HOU ; Bobiao NING ; Shanshan YE ; Mengyu LIU ; Yipeng SHI ; Danyu LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):58-67
ObjectiveTo investigate the mechanism by which Mingshi prescription regulates the retinal melanopsin-dopamine (Opn4-DA) axis in myopic mice to inhibit endoplasmic reticulum (ER) stress in the retina and sclera, thereby delaying axial elongation associated with myopia. MethodsSixty 4-week-old male SPF-grade C57BL/6J mice were randomly divided into a normal group, a form-deprived myopia group (FDM group), an intrinsically photosensitive retinal ganglion cells ablation group (ipRGCs group), a Mingshi Prescription group (MSF group, 5.2 g·kg-1), and an ipRGCs + MSF group (5.2 g·kg-1). Except for the normal group, all other groups underwent FDM modeling. Additionally, the ipRGCs and ipRGCs + MSF groups received retinal ipRGC ablation. Three weeks after modeling, the MSF and ipRGCs + MSF groups were administered Mingshi prescription via continuous gavage for six weeks. After refraction and axial length were measured in all mice, eyeballs were collected along with retinal and scleral tissues. Pathological and morphological changes in the retina, choroid, and sclera were observed using periodic acid-Schiff (PAS) staining. Western blot was employed to detect the relative protein expression levels of dopamine D1 receptor (DRD1), C/EBP homologous protein (CHOP), and glucose-regulated protein 78 (GRP78) in the retina, and CHOP and GRP78 in the sclera. Real-time PCR was used to detect the relative mRNA expression of Opn4, CHOP, and GRP78 in the retina, and CHOP and GRP78 in the sclera. Immunofluorescence staining (IF) was performed to detect the expression of Opn4 and DRD1 in retinal tissues. ResultsCompared with the normal group, the FDM group showed a significant myopic shift in refraction (P<0.05) and a significant increase in axial length (P<0.05). The retinal layers were thinner, the number of ganglion cells was reduced, and collagen fibers in the sclera were loosely arranged with evident gaps. Opn4 and DRD1 protein and mRNA expression in the retina were significantly decreased (P<0.05), while CHOP and GRP78 protein and mRNA expression in both retinal and scleral tissues were significantly increased (P<0.05). Compared with the FDM group, the ipRGCs group exhibited further increases in myopic refraction and axial length (P<0.05), more pronounced thinning and looseness in the retinal, choroidal, and scleral layers, lower expression of Opn4 and DRD1 protein and mRNA in the retina (P<0.05), and higher expression of CHOP and GRP78 protein and mRNA in the retina and sclera (P<0.05). Compared with the FDM group, the MSF group showed significantly reduced refractive error and axial length (P<0.05), with improved cellular number, arrangement, and thickness in ocular tissues, increased Opn4 and DRD1 protein and mRNA expression in the retina (P<0.05), and reduced CHOP and GRP78 protein and mRNA expression in both retina and sclera (P<0.05). Similarly, the ipRGCs + MSF group showed significant improvements in terms of the above items compared with the ipRGCs group (P<0.05). ConclusionMingshi Prescription delays myopic axial elongation and refractive progression by regulating the Opn4-DA axis in the retina of myopic mice, thereby inhibiting ER stress in the retina and sclera. This intervention promotes Qi and blood nourishment of the eyes, softens the fascia, and restores ocular rhythm.
2.Locally producing antibacterial peptide to deplete intratumoral pathogen for preventing metastatic breast cancer.
Shizhen GENG ; Tingting XIANG ; Yaru SHI ; Mengnian CAO ; Danyu WANG ; Jing WANG ; Xinling LI ; Haiwei SONG ; Zhenzhong ZHANG ; Jinjin SHI ; Junjie LIU ; Airong LI ; Ke SUN
Acta Pharmaceutica Sinica B 2025;15(2):1084-1097
Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.
3.Prognostic value of neutrophil-to-lymphocyte ratio and glycemic variability in patients with sepsis
Danyu LI ; Jiali YAO ; Hongjie TONG ; Kun CHEN
China Modern Doctor 2025;63(5):53-56
Objective To investigate the prognostic value of neutrophil-to-lymphocyte ratio(NLR)and glycemic variability(GV)in patients with sepsis.Methods A total of 121 sepsis patients hospitalized in Jinhua Central Hospital from January 2023 to January 2024 were selected and divided into survival group(n=68)and death group(n=53)according to whether they died within 28d of confirmed sepsis.Blood glucose levels on the first 1-3 days after the diagnosis of sepsis were collected,and GV was calculated.The risk factors impacting the prognosis of patients with sepsis were analyzed through binary Logistic regression.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of relevant indicators.Results Compared with survival group,the levels of neutrophil count,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ),procalcitonin,NLR and GV levels in death group were significantly increased(P<0.05),while lymphocyte was decreased(P<0.05).Logistic regression analysis indicated that NLR and GV might be independent risk factors affecting the prognosis of sepsis patients(P<0.05).ROC curve showed area under the curve(AUC)of NLR was 0.814 and GV AUC was 0.805.Conclusion NLR and GV could potentially be independent risk factors affecting the prognosis of sepsis patients,and they hold a certain degree of predictive worth for the prognosis of sepsis patients.
4.Elevated levels of serum PKM2,Gal-3 and CitH3 could predict pulmonary infection complicated by mechanical ventilation
Hangdong HUANG ; Danyu LI ; Xiaofeng ZHU
Basic & Clinical Medicine 2025;45(1):86-90
Objective To investigate the relationship between serum level of pyruvate kinase M2(PKM2),galec-tin-3(Gal-3)and citrolinated histone H3(CitH3)and pulmonary infection in patients with mechanical ventilation(MV).Methods A total of 120 patients with MV admitted to Jinhua Central Hospital from October 2022 to March 2024 were included in the study.They were divided into pulmonary infection group(n=50)and non-pulmonary in-fection group(n=70).Serum level of PKM2,Gal-3 and CitH3 was detected by ELISA.The patients were divided into good prognosis group(n=79)and bad prognosis group(n=41).Multivariate Logistic regression analysis was performed to analyze the factors affecting the adverse prognosis of MV patients.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum PKM2,Gal-3 and CitH3 for poor prognosis in pa-tients undergoing MV.Results Compared with non-pulmonary infection group,serum level of PKM2,Gal-3 and CitH3 in pulmonary infection group was increased(P<0.05).The level of serum PKM2,Gal-3 and CitH3 in the poor prognosis group was increased(P<0.05).The Clinical Pulmonary Infection score(CPIS)of the poor progno-sis group was higher than that of the good prognosis group(P<0.05).PKM2,Gal-3 and CitH3 were all risk factors for poor prognosis in MV patients(P<0.05).The area under the curve(AUC)of PKM2,Gal-3,CitH3 and com-bined prediction of poor prognosis were 0.712,0.839,0.779 and 0.925,respectively.AUC of combined diagnosis of PKM2,GAL-3,CITH3 and combined diagnosis was better than that of single detection(Z=4.261,2.521,3.676,P<0.001,0.05,0.001).Conclusions The serum level of PKM2,Gal-3,and CitH3 in MV patients with concurrent pulmonary infections is found to be higher than those in those without pulmonary infections,so these three factors have potential predictive value for poor prognosis of MV patients.
5.Gao Jiansheng's Experience in Differentiating and Treating Herpes Simplex Keratitis Based on the Theory of Hidden Pathogens
Xi CHEN ; Yina CHEN ; Xiaonan YANG ; Danyu LI ; Wei YANG
Journal of Traditional Chinese Medicine 2025;66(5):448-452
This paper summarizes Professor Gao Jiansheng's clinical experience in treating herpes simplex keratitis (HSK) based on the theory of hidden pathogens. It is believed that the core pathogenesis of HSK involves deficiency of vital qi and the internal presence of pathogenic factors. In the early stage, the pathogenesis is characterized by lung and spleen qi deficiency and invasion of external pathogens. In the middle stage, pathogenesis worsens due to latent pathogens damaging the vital qi and spleen deficiency with dampness. In the late stage, kidney yang deficiency and lingering pathogenic toxins are the root cause of recurrent attacks. In clinical practice, it is recommended to strengthen and protect the vital qi. In the early stage, the Modified Yupingfeng Powder (玉屏风散) is used. In the middle stage, the Modified Linggui Zhugan Decoction (苓桂术甘汤) is used. In the late stage, a self-formulated Modified Bushen Tuodu Fomulation (补肾托毒方) is applied. Additionally, herbs of tonifying qi and strengthening the exterior are used throughout the treatment to reduce recurrence.
6.Research progress on the pathogenesis and treatment of benign essential blepharospasm
Xi CHEN ; Wei YANG ; Danyu LI ; Xiaonan YANG ; Yina CHEN
International Eye Science 2025;25(7):1105-1110
Benign essential blepharospasm(BEB)is a neurological disorder characterized by involuntary contractions of periocular muscles, which can lead to functional blindness and significantly impair patients' quality of life. This article systematically reviews the epidemiology, clinical manifestations, pathogenesis, and therapeutic advances in BEB. Epidemiological data indicate that the global prevalence of BEB is approximately 1 in 200000, with a predilection for individuals over 50 years of age and a significantly higher incidence in female than in male. The exact pathogenesis of BEB remains incompletely understood, though current evidence suggests close associations with neurotransmitter dysfunction, reduced cortical inhibition, and genetic susceptibility. Therapeutic strategies primarily focus on symptomatic management. Botulinum toxin type A(BTX-A)injection remains the first-line treatment but requires repeated administrations due to transient efficacy. Other treatments, including oral drugs, surgery, and repetitive transcranial magnetic stimulation, also have major limitations. By synthesizing recent research progress from domestic and international studies, this review aims to provide novel insights for the clinical management of BEB, ultimately improving patient outcomes.
7.Constructing an induction educational system for clinical rotations in standardized pediatric residency training: program development and outcome evaluation
Ying LIAO ; Wei BAI ; Shan LI ; Guo YU ; Danyu SONG ; Hui YAN
Chinese Journal of Medical Education Research 2025;24(4):440-445
Objective:To construct a multimodal induction educational system suitable for standardized pediatric residency training bases, and to evaluate its effectiveness, thereby obtaining suggestions for further improvement.Methods:Twelve residents newly enrolled in the 2023 standardized residency training program who commenced their first-year training were included as study subjects. The induction educational system comprised multiple modules: department introduction, training plan and assessment requirements, departmental workflow, routine diagnosis and treatment of major diseases, specialized skills/procedures, and lifestyle guidance. Training materials and methods were tailored to the characteristics of each training module. Checklists were used for supervision and review, and a competency checklist was designed to evaluate residents' mastery of the training at two weeks of induction, which would guarantee the effectiveness of the training. A questionnaire survey, powered by wjx.cn, was used to obtain the experience and suggestions from the residents and ward instructors on induction education, and content ranking analysis was performed on the survey results.Results:The survey revealed that, before starting a new rotation, residents' top three educational needs were departmental workflow, routine diagnosis and treatment of common diseases, and specialized skills/procedures. Residents preferred face-to-face lectures and demonstrations by attending physicians or senior residents; instructors suggested improving relevant materials (such as resident physician manuals and video materials) and face-to-face lectures. The residents considered the current induction educational system to be greatly beneficial in basic theories, treatment principles, basic skills, and auxiliary examination processes.Conclusions:Through the above research, a multimodal induction educational system suitable for the standardized pediatric residency training base in the Peking University First Hospital has been preliminarily established, and suggestions for further improvement have been obtained, which is conducive to further improving the system and residents' post competency.
8.The relationship between multiple elements in urine and arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region
Yuchen GUO ; Binggan WEI ; Fan ZHAO ; Xinye LI ; Rui WANG ; Shuhui YIN ; Nan WU ; Lingling HE ; Zhen DI ; Kaiwen LIU ; Wei SONG ; Hui WANG ; Zhongbing ZHANG ; Danyu DENG ; Zhiwei GUO
Chinese Journal of Endemiology 2025;44(7):535-542
Objective:To study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.
9.Establishment of an indicator system for entrustable professional activities in general practice stage of pediatric specialist physician training
Shan LI ; Danyu SONG ; Xifang RU ; Xiaoyu LIU ; Lili LIU ; Xin QI ; Mi YAO ; Jianguang QI
Chinese Journal of Medical Education Research 2025;24(4):466-472
Objective:To construct an indicator system for entrustable professional activities (EPAs) in the general practice enhancement stage of pediatric specialist physician training.Methods:A draft indicator system for EPAs in the general practice enhancement stage of pediatric physician training was developed through core EPAs working group discussion, literature review, nominal group discussion, and expert consultation. Subsequently, the indicator system was preliminarily implemented and revised.Results:The core EPAs working group consisted of nine specialist physician trainers. In the initial brainstorming stage, a "potential list" of 30 activities was established. After literature review and collation, the draft indicator system included eight EPAs. Through nominal group discussion, the connotation of the draft was enriched, and the importance of the EPAs was ranked and modified. Finally, through expert consultation, the EPAs for the general practice enhancement stage of pediatric specialist physician training were determined. These included basic operations for the treatment of critically ill children, identification and management of critical illnesses, referral of critically ill children, perioperative management, in-hospital consultation, medical and teaching management and system improvement, doctor-patient communication and dispute handling, and response to public health events. During the preliminary implementation stage, a total of nine specialist physicians who participated in the training were evaluated. Based on the problems found in the pre-evaluation, the indicators of EPAs were revised, and a corresponding curriculum training system was developed.Conclusions:Through multiple rounds of nominal group discussion and expert consultation, the indicator system for EPAs in the general practice enhancement stage of pediatric specialist physician training was formulated. The system was preliminarily implemented and revised, and a curriculum system was constructed.
10.Analysis of influencing factors of adult dental fluorosis in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region in 2024
Fan ZHAO ; Zhong YANG ; Kaifeng XU ; Fenxia LI ; Shifang ZHANG ; Xinye LI ; Cong LIU ; Mengxin LI ; Yuchen GUO ; Tianrui ZHUANG ; Ke LI ; Zhixian YANG ; Danyu DENG ; Zhongbing ZHANG ; Zhiwei GUO
Chinese Journal of Endemiology 2025;44(3):232-236
Objective:To investigate the influencing factors of adult dental fluorosis in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.Methods:A case-control study was conducted in January 2024 to select adult fluorosis patients (case group) and healthy individuals (control group) from the drinking water-borne endemic fluorosis areas in Helinger County, Hohhot City, Inner Mongolia Autonomous Region as the survey subjects. Urine samples were collected to determine urinary fluoride concentration. A questionnaire survey was conducted. SPSS 25.0 software was used for χ 2 test and multivariate logistic regression analysis. Restricted cubic spline (RCS) was used to analyze the association between urinary fluoride concentration and the risk of dental fluorosis in adults. Results:A total of 161 individuals were included in the survey, including 100 in the case group and 61 in the control group. The results of univariate analysis showed that there were statistically significant differences in the distribution of gender, smoking, and urinary fluoride concentration between the case group and the control group (χ 2 = 7.54, 5.02, 9.69, P < 0.05). The results of multivariate logistic regression analysis indicated that gender ( OR = 0.36, 95% CI: 0.18 - 0.73, P = 0.005) and urinary fluoride concentration ( OR = 3.08, 95% CI: 1.46 - 6.67, P = 0.003) were the influencing factors of adult fluorosis. RCS analysis showed a significant linear dose-response relationship between the risk of dental fluorosis and urinary fluoride concentration ( Poverall trend = 0.001, Pnonlinear = 0.071). When the urinary fluoride concentration was greater than 1.57 mg/L, the risk of dental fluorosis increased with the increase of urinary fluoride concentration. Conclusion:Gender and urinary fluoride concentration are the risk factors of dental fluorosis in adults in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.

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