1.Establishment and Evaluation of Insomnia Animal Models with Heart and Spleen Deficiency
Jieyao DIAO ; Hui XU ; Yunfeng ZHOU ; Zhen WANG ; Xin ZHAO ; Haoguang QU ; Chongyang GUAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):234-243
		                        		
		                        			
		                        			Heart and spleen deficiency syndrome is the most common syndrome type in patients with insomnia. Based on the theory of disease syndrome-combined animal model, this paper used multiple databases to search for the keywords "heart and spleen deficiency", "insomnia", "sleepless", "disease syndrome-combined animal model", "model evaluation", etc. It selected the literature related to the animal model of insomnia with heart and spleen deficiency in the past 20 years to evaluate from the aspects of model establishment, modeling factors, syndrome model, disease model, macro characterization & macro characterization evaluation scale, micro indicators, etc. It is found that the existing animal model of insomnia with heart and spleen deficiency is not completely constructed by the method of disease syndrome combination of disease modeling factors and syndrome modeling factors. In the model using this method, the single establishment factor of heart and spleen deficiency does not conform to the clinical reality of disease, and the selection of the factors for the insomnia model is not closely related to or even separated from the syndrome performance. There is a problem of insufficient quantification of macro representation when the macro representation of the model replaces the symptoms related to heart and spleen deficiency syndrome and insomnia in an equivalent manner for macro representation evaluation, which can be improved according to the quantitative ideas and examples of the existing macro representation and macro representation evaluation scale. There are few specific indicators of heart and spleen deficiency syndrome in micro indicators. The micro research of heart and spleen deficiency syndrome and the essence of other traditional Chinese medicine (TCM) syndromes can be carried out by metabonomics and other technologies combined with the theory of corresponding prescription and syndrome, along the specific related ideas of "prescription and syndrome, treatment principle and selection of prescription, treatment principle and selection of acupoints, as well as therapeutic mechanism and syndrome essence". The future users and researchers of animal models of insomnia with heart and spleen deficiency can get improved methods and ideas through the shortcomings of animal models of heart and spleen deficiency listed in this paper and construct animal models of insomnia with heart and spleen deficiency that are more suitable for clinical practice, so as to establish a more perfect modeling method and evaluation system of disease syndrome-combined animal model. 
		                        		
		                        		
		                        		
		                        	
2.Establishment and Evaluation of Insomnia Animal Models with Heart and Spleen Deficiency
Jieyao DIAO ; Hui XU ; Yunfeng ZHOU ; Zhen WANG ; Xin ZHAO ; Haoguang QU ; Chongyang GUAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):234-243
		                        		
		                        			
		                        			Heart and spleen deficiency syndrome is the most common syndrome type in patients with insomnia. Based on the theory of disease syndrome-combined animal model, this paper used multiple databases to search for the keywords "heart and spleen deficiency", "insomnia", "sleepless", "disease syndrome-combined animal model", "model evaluation", etc. It selected the literature related to the animal model of insomnia with heart and spleen deficiency in the past 20 years to evaluate from the aspects of model establishment, modeling factors, syndrome model, disease model, macro characterization & macro characterization evaluation scale, micro indicators, etc. It is found that the existing animal model of insomnia with heart and spleen deficiency is not completely constructed by the method of disease syndrome combination of disease modeling factors and syndrome modeling factors. In the model using this method, the single establishment factor of heart and spleen deficiency does not conform to the clinical reality of disease, and the selection of the factors for the insomnia model is not closely related to or even separated from the syndrome performance. There is a problem of insufficient quantification of macro representation when the macro representation of the model replaces the symptoms related to heart and spleen deficiency syndrome and insomnia in an equivalent manner for macro representation evaluation, which can be improved according to the quantitative ideas and examples of the existing macro representation and macro representation evaluation scale. There are few specific indicators of heart and spleen deficiency syndrome in micro indicators. The micro research of heart and spleen deficiency syndrome and the essence of other traditional Chinese medicine (TCM) syndromes can be carried out by metabonomics and other technologies combined with the theory of corresponding prescription and syndrome, along the specific related ideas of "prescription and syndrome, treatment principle and selection of prescription, treatment principle and selection of acupoints, as well as therapeutic mechanism and syndrome essence". The future users and researchers of animal models of insomnia with heart and spleen deficiency can get improved methods and ideas through the shortcomings of animal models of heart and spleen deficiency listed in this paper and construct animal models of insomnia with heart and spleen deficiency that are more suitable for clinical practice, so as to establish a more perfect modeling method and evaluation system of disease syndrome-combined animal model. 
		                        		
		                        		
		                        		
		                        	
3.Inhibition of HDAC3 Promotes Psoriasis Development in Mice Through Regulating Th17
Fan XU ; Xin-Rui ZHANG ; Yang-Chen XIA ; Wen-Ting LI ; Hao CHEN ; An-Qi QIN ; Ai-Hong ZHANG ; Yi-Ran ZHU ; Feng TIAN ; Quan-Hui ZHENG
Progress in Biochemistry and Biophysics 2025;52(4):1008-1017
		                        		
		                        			
		                        			ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4+ T lymphocytes, CD8+ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4+ T lymphocytes. Additionally, spleen CD4+ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4+ and CD8+ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4+ and CD8+ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4+ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4+ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6. 
		                        		
		                        		
		                        		
		                        	
4. Mechanism and experimental validation of Zukamu granules in treatment of bronchial asthma based on network pharmacology and molecular docking
Yan-Min HOU ; Li-Juan ZHANG ; Yu-Yao LI ; Wen-Xin ZHOU ; Hang-Yu WANG ; Jin-Hui WANG ; Ke ZHANG ; Mei XU ; Dong LIU ; Jin-Hui WANG
Chinese Pharmacological Bulletin 2024;40(2):363-371
		                        		
		                        			
		                        			 Aim To anticipate the mechanism of zuka- mu granules (ZKMG) in the treatment of bronchial asthma, and to confirm the projected outcomes through in vivo tests via using network pharmacology and molecular docking technology. Methods The database was examined for ZKMG targets, active substances, and prospective targets for bronchial asthma. The protein protein interaction network diagram (PPI) and the medication component target network were created using ZKMG and the intersection targets of bronchial asthma. The Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene ontology (GO) were used for enrichment analysis, and network pharmacology findings were used for molecular docking, ovalbumin (OVA) intraperitoneal injection was used to create a bronchial asthma model, and in vivo tests were used to confirm how ZKMG affected bronchial asthma. Results There were 176 key targets for ZKMG's treatment of bronchial asthma, most of which involved biological processes like signal transduction, negative regulation of apoptotic processes, and angiogenesis. ZKMG contained 194 potentially active components, including quercetin, kaempferol, luteolin, and other important components. Via signaling pathways such TNF, vascular endothelial growth factor A (VEGFA), cancer pathway, and MAPK, they had therapeutic effects on bronchial asthma. Conclusion Key components had strong binding activity with appropriate targets, according to molecular docking data. In vivo tests showed that ZKMG could reduce p-p38, p-ERKl/2, and p-I 
		                        		
		                        		
		                        		
		                        	
		                				5.A new pyrazine from Hypecoum erectum  L. 
		                			
		                			Yun LIU ; Meng-ya HU ; Wen-jing ZHANG ; Yu-xin FAN ; Rui-wen XU ; Deng-hui ZHU ; Yan-jun SUN ; Wei-sheng FENG ; Hui CHEN
Acta Pharmaceutica Sinica 2024;59(1):183-187
		                        		
		                        			
		                        			 Four pyrazines were isolated from the 
		                        		
		                        	
6.The role of age and body mass index on cancer occurrence in a hypertensive population:a retrospective cohort study
Xin-Yue GUO ; Jia-Huan PENG ; Hui-Lin XU ; Yong-Fu YU ; Guo-You QIN
Fudan University Journal of Medical Sciences 2024;51(1):12-18
		                        		
		                        			
		                        			Objective To analyze the combined effect of body mass index(BMI)and age with cancer occurrence among a hypertensive population in Minhang District,Shanghai.Methods Participants of this study were 212 394 hypertensive patients without cancer in Minhang District,Shanghai,registered in the electronic health information system from 2007 to 2015.Age and BMI were included as smoothing functions in the generalized additive Cox proportional risk model.The bivariate response model was constructed to visualize results using surface plots and to comprehensively analyze the association of BMI and age with the risk of cancer occurrence.Results A total of 22 141 participants developed cancer by Dec 31,2018.The association between age and the risk of cancer incidence showed an overall linear trend while the association between BMI and the risk of cancer incidence showed an overall"U"shape.BMI at about 26 kg/m2 showed the lowest risk of cancer incidence.The risk of cancer occurrence increased with increasing age in people with different BMIs.The associations between BMI and the risk of cancer incidence were different at different age groups:there was no significant association between BMI and the risk of cancer incidence in the young people(20-44 years).While in the middle-aged and older people aged over 45 years,BMI was associated with the risk of cancer incidence in a"U"shape.The lowest risk of cancer incidence was around the BMI of 26 kg/m2.Conclusion BMI among the population with hypertension should be controlled in a reasonable range,especially in the middle-aged and older population,to prevent cancer occurrence.
		                        		
		                        		
		                        		
		                        	
7.Analysis of HPV infection and genotype distribution among 1 658 male reproductive health outpatients
Nazhakaiti ABUDUKELIMU ; Jian-Hui LI ; Tian-Cheng ZHANG ; Xin WANG ; Zhi-Ming XU ; Qian-Xi ZHU
Fudan University Journal of Medical Sciences 2024;51(1):69-75
		                        		
		                        			
		                        			Objective To investigate the human papillomavirus(HPV)infection and genotype distribution characteristics among male reproductive health outpatients,and to compare the differences among different age groups of outpatients.Methods A total of 1 658 males,visited in the Affiliated Hospital of Shanghai Institute of Planned Parenthood Research from 2018 to 2022,were selected and 23 HPV genotypes were detected by PCR-reverse dot hybridization.Results Among the 1 658 subjects,the overall HPV infection rate was 22.50%.Single infection accounted for 66.76%,which was the main infection type.HPV infection among different age groups were statistically significant(P<0.001),with HPV infection of 16.83%,22.87%,34.63%,and 29.35%for 18-30,31-40,41-50,and≥51 years,respectively.The top 5 high risk HPV genotypes were HPV52(3.56%),HPV16(3.26%),HPV39(2.41%),HPV51(2.17%),HPV58(2.17%),and the top 1 low risk HPV genotype was HPV81(2.90%).The proportions of infected individuals in this study that could be completely covered by bivalent,quadrivalent,and nine-valent HPV vaccines were 7.77%,12.33%,and 26.27%,respectively.Conclusion The predominant infection type among male reproductive health outpatients was single infection type.HPV 52,16,39,51 and 58 were the most common high risk genotypes,while HPV 81 was the most common low risk genotype.Individuals aged 41-50 years had the highest HPV infection rate.
		                        		
		                        		
		                        		
		                        	
8.Application of 3.0T HR-MRI technique in AIS and an analysis on the influence factors of prognosis
Haina XU ; Hui LIANG ; Zhenping WANG ; Zhihui FENG ; Yingman ZHAO ; Jian ZHONG ; Xin QIN
China Medical Equipment 2024;21(1):63-68
		                        		
		                        			
		                        			Objective:To investigate the application of 3.0T high resolution magnetic resonance imaging(HR-MRI)in acute ischemic stroke(AIS)and the influence factors of prognosis.Methods:A total of 92 AIS patients who underwent treatment in Hainan General Hospital from January 2019 to June 2022 were selected as the research objects.All patients were treated by thrombolytic therapy,and they were divided into favorable prognosis group(mRS scores≤2 points,n=66)and poor prognosis group(mRS score>2 points,n=26)according to modified Rankin Scale after they received 90d treatment.All of patients underwent Magnetom Trio type of 3.0 T HR-MRI examination within 1 week after they hospitalized,and the changes of luminal stenosis rate,the luminal area at the narrowest point,the plaque load,T2WIsignal intensity index,T1WI signal intensity index,plaque enhancement rate and other parameters were compared.The receiver operating characteristics(ROC)curve was adopted to analyze the predictive value of 3.0T HR-MRI parameters on the AIS prognosis.Binary Logistic regression model was used to analyze the risk factors that affected the prognosis of AIS patients.Results:The difference of infarction diameter between two groups was statistically significant(x2=6.574,P<0.05).The lumen area at the narrowest point in the poor prognosis group was significantly lower than that in the favorable prognosis group,while the T2WI signal intensity index,T1WI signal intensity index and plaque enhancement rate in the poor prognosis group were significantly higher than those in the favorable prognosis group(t=-3.378,4.443,4.413,3.890,P<0.05),respectively.ROC curve analysis showed that the area under curve(AUC)values of T2WI signal intensity index,T1WI signal intensity index,lumen area at the narrowest point and plaque enhancement rate in predicting the AIS prognosis were respectively 0.743,0.739,0.706 and 0.748.The Logistic regression analysis showed that infarction diameter>3.0cm,T1WI signal intensity index,T2WI signal intensity index,lumen area at the narrowest point and plaque enhancement rate were respectively independent risk factors that could affect AIS prognosis(OR=3.889,257.151,105.073,4.091,1.121,P<0.05).Conclusion:3.0T HR-MRI has higher efficiency in the assessment for the prognosis of patients with AIS,which can provide guidance for the judgement of prognosis and the formulation of treatment scheme through observes the changes of a series of parameters include T2WI signal strength index,T1WI signal strength index,the lumen area at the narrowest point,plaque enhancement rate.The above parameters are risk factors that affect the prognosis of patients,which often represent the progress of patients'conditions.
		                        		
		                        		
		                        		
		                        	
9.Prognosis and its influencing factors in patients with non-gastric gastrointestinal stromal tumors at low risk of recurrence: a retrospective multicenter study in China
Linxi YANG ; Weili YANG ; Xin WU ; Peng ZHANG ; Bo ZHANG ; Junjun MA ; Xinhua ZHANG ; Haoran QIAN ; Ye ZHOU ; Tao CHEN ; Hao XU ; Guoli GU ; Zhidong GAO ; Gang ZHAI ; Xiaofeng SUN ; Changqing JING ; Haibo QIU ; Xiaodong GAO ; Hui CAO ; Ming WANG
Chinese Journal of Gastrointestinal Surgery 2024;27(11):1123-1132
		                        		
		                        			
		                        			Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.
		                        		
		                        		
		                        		
		                        	
		                				10.Research on three-dimensional ordered porous carbon-based materials prepared from Acanthopanax senticosus  traditional Chinese medicine residues and their drug loading performance
		                			
		                			De-sheng WANG ; Jia-xin FAN ; Ri-qing CHENG ; Shi-kui WU ; Lai-bing WANG ; Jia-hao SHI ; Ting-ting CHEN ; Qin-fang HE ; Chang-jin XU ; Hui-qing GUO
Acta Pharmaceutica Sinica 2024;59(10):2857-2863
		                        		
		                        			
		                        			 Three-dimensional ordered porous carbon materials exhibit potential application prospects as excellent drug supports in drug delivery systems due to their high specific surface area, tunable pore structure, and excellent biocompatibility. In this study, three-dimensional ordered porous carbon materials were prepared using 
		                        		
		                        	
            
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