1.Chinese Materia Medica by Regulating Nrf2 Signaling Pathway in Prevention and Treatment of Ulcerative Colitis: A Review
Yasheng DENG ; Lanhua XI ; Yanping FAN ; Wenyue LI ; Tianwei LIANG ; Hui HUANG ; Shan LI ; Xian HUANG ; Chun YAO ; Guochu HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):321-330
		                        		
		                        			
		                        			Ulcerative colitis(UC) is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulceration of the colonic mucosa and submucosa, and its complex pathogenesis involves immune abnormality, oxidative stress and other factors. The nuclear transcription factor E2-related factor 2(Nrf2), encoded by the Nfe212 gene, plays a central role in antioxidant responses. It not only activates various antioxidant response elements such as heme oxygenase-1(HO-1) and quinone oxidoreductase 1(NQO1), but also enhances the activity of glutathione-S-transferase(GST) and superoxide dismutase 1(SOD1), effectively eliminating reactive oxygen species(ROS) accumulated in the body, and mitigating oxidative stress-induced damage to intestinal mucosa. In addition, Nrf2 can reduce the release of inflammatory factors and infiltration of immune cells by regulating immune response, cell apoptosis and autophagy pathways, thereby alleviating intestinal inflammation and promoting the repair and regeneration of damaged mucosa. Based on this, this paper reviews the research progress of Chinese materia medica in the prevention and treatment of UC by modulating the Nrf2 signaling pathway. It deeply explores the physiological role of Nrf2, the molecular mechanism of activation, the protective effect in the pathological process of UC, and how active ingredients in Chinese materia medica regulate the Nrf2 signaling pathway through multiple pathways to exert their potential mechanisms. These studies have revealed in depth that Chinese materia medica can effectively combat oxidative stress by regulating the Nrf2 signaling pathway. It can also play a role in anti-inflammatory, promoting autophagy, inhibiting apoptosis, protecting the intestinal mucosal barrier, and promoting intestinal mucosal repair, providing new ideas and methods for the multi-faceted treatment of UC. 
		                        		
		                        		
		                        		
		                        	
2.Association of parenting style with emotional and behavioral problems in preschool children
LIANG Xi, LI Ruoyu, FANG Jiao, WANG Xiaoyan, WANG Yuhui
Chinese Journal of School Health 2025;46(9):1266-1271
		                        		
		                        			Objective:
		                        			To explore the effects of parenting style on emotional and behavioral problems (EBPs) of preschool children and to provide theoretical reference for promoting children s physical and mental health.
		                        		
		                        			Methods:
		                        			In October-November 2021, a stratified cluster random sampling method was adopted to select 3 575 preschool children aged 3-6 years from 12 kindergartens in Hefei. Data on parenting styles and children s EBPs were collected through electronic questionnaires. Binary Logistic regression model was used to explore the effects of parenting styles on children s EBPs.
		                        		
		                        			Results:
		                        			The detection rates of emotional symptoms, conduct problems, hyperactivity, peer interaction problems, and prosocial behavior problems were 15.5% ( n =554), 23.2% ( n =830), 22.4% ( n =802), 38.2% ( n =1 367), and 29.5% ( n =1 055) in preschool children, respectively. Binary Logistic regression analysis showed that after adjusting for covariates such as child s age, sex, and preterm birth, a high authoritative parenting style reduced the risk of EBPs in children ( OR =0.29-0.78), while a high authoritarian ( OR =1.36-2.15) and high permissive ( OR =1.36-1.68) parenting style in mothers increased the risk of EBPs in children (all  P <0.05). Further stratified analysis indicated that among children with fathers exhibiting high authoritative, high authoritarian, or high permissive parenting styles, a high authoritative parenting style in mothers reduced the risk of peer interaction problems and prosocial behavior problems ( OR =0.51,  0.30 ; 0.44, 0.23; 0.51, 0.29, all  P <0.05). Among children with fathers exhibiting a high authoritative parenting style, a high authoritarian parenting style in mothers increased the risk of emotional problems ( OR =2.59), and both high authoritarian and high permissive parenting styles in mothers increased the risk of conduct problems ( OR =3.25, 2.09) and hyperactivity problems ( OR =2.35, 2.87) (all  P <0.05). Among children with fathers exhibiting high authoritarian or high permissive parenting styles, a high authoritarian parenting style in mothers increased the risk of EBPs ( OR =1.65-2.71, 1.62-2.52, all  P <0.05).
		                        		
		                        			Conclusion
		                        			Parenting style is an important factor affecting EBPs of preschool children, and appropriate parenting style is beneficial for children s psychological development.
		                        		
		                        		
		                        		
		                        	
3.Preliminary Efficacy of Growth Hormone Therapy in Children With Congenital HeartDisease and Short Stature: A Six-case Report and Literature Review
Xi YANG ; Siyu LIANG ; Qianqian LI ; Hanze DU ; Shuaihua SONG ; Yue JIANG ; Huijuan MA ; Shi CHEN ; Hui PAN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):641-646
Congenital heart disease (CHD) is a congenital malformation resulting from abnormal embryonic development of the heart and great vessels, accounting for approximately 25% of all congenital malformations. Children with CHD are often complicated by short stature. Although surgical treatment can improve their growth and development to a certain extent, some children still experience growth retardation after surgery. Recombinant human growth hormone (rhGH) is the main drug for treating short stature, but its efficacy and safety in the treatment of patients with concomitant CHD warrant further investigation. This article reports six cases of children with CHD and short stature who were treated with rhGH. Through a literature review, we summarize and discuss the therapeutic efficacy, follow-up experiences, and adverse reactions of rhGH treatment, aiming to provide references for clinicians in applying rhGH to treat patients with CHD and short stature.
4.Impact of pembrolizumab combined with chemotherapy on angiogenesis and circulating endothelial cells in patients with advanced non-small cell lung cancer
Xi JIANG ; Yongcun WU ; Yan LIANG ; Li CHU ; Yingxin DUAN ; Lijun WANG ; Junjie HUO
Journal of International Oncology 2024;51(2):89-94
		                        		
		                        			
		                        			Objective:To explore the impact of pembrolizumab combined with chemotherapy on angiogenesis and circulating endothelial cells in patients with advanced non-small cell lung cancer (NSCLC) .Methods:The retrospective analysis of clinical data from 121 patients diagnosed with advanced NSCLC who were admitted to the Second Affiliated Hospital of Xingtai Medical College from August 2021 to January 2023 was conducted. These patients were divided into a control group ( n=57) and an observation group ( n=64) based on the designated treatment protocol. Specifically, individuals in the control group received standard chemotherapy (cisplatin+paclitaxel), while those in the observation group underwent penpilimab therapy in conjunction with conventional chemotherapy. The comparative assessment encompassed short-term clinical efficacy, quality of life, immune function parameters, angiogenic factors [including endostatin, insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF) ], circulating endothelial cells, and adverse reactions within the two groups. Results:After 6 courses of treatment, the objective response rate [67.19% (43/64) vs. 49.12% (28/57) ] and disease control rate [87.50% (56/64) vs. 70.18% (40/57) ] in observation group were higher than those in control group, with statistically significant differences ( χ2=4.06, P=0.044; χ2=5.52, P=0.019). The quality of life score of observation group [ (56.77±6.81) points] was significantly higher than that of control group [ (47.73±8.23) points], with a statistically significant difference ( t=6.61, P<0.001) ; The T cell subgroup CD3 + levels [ (63.59±9.00) % vs. (53.06±8.80%), t=6.49, P<0.001], CD4 + levels [ (46.54±8.20) % vs. (30.74±7.32) %, t=11.13, P<0.001] and CD4 +/CD8 + ratio (1.90±0.36 vs. 1.21±0.28, t=11.66, P<0.001) in observation group were significantly higher than those in control group, with statistically significant differences; Endostatin in observation group [ (48.99±3.43) μmol/L] was significantly higher than that in control group [ (31.35±3.87) μmol/L], with a statistically significant difference ( t=26.58, P<0.001), IGF-1 [ (102.31±20.35) μg/L vs. (134.98±19.02) μg/L] and VEGF [ (31.70±4.32) pg/ml vs. (58.71±5.99) pg/ml] were significantly lower in observation group than those in control group, with statistically significant differences ( t=18.73, P<0.001; t=28.14, P<0.001). The number of circulating endothelial cells in observation group [ (58.77±10.03) /ml] was significantly lower than that in control group [ (87.01±8.01) /ml], with a statistically significant difference ( t=17.20, P<0.001). During treatment, there were no statistically significant differences in the incidence of gastrointestinal reaction ( χ2=0.01, P=0.908), leukopenia ( χ2=0.64, P=0.424), thrombocytopenia ( χ2=0.28, P=0.597), anemia ( χ2=1.66, P=0.197), nephrotoxicity ( χ2=0.64, P=0.424), skin rash ( χ2=1.33, P=0.249) between the two groups. Conclusion:The combination therapy of pembrolizumab and chemotherapy for the treatment of advanced NSCLC has demonstrated noteworthy effectiveness. This regimen has the potential to enhance patients' immune functionality, ameliorate their overall quality of life, suppress angiogenesis, and exhibits a commendable profile of safety and reliability.
		                        		
		                        		
		                        		
		                        	
5.Prognosis and influencing factors analysis of patients with initially resectable gastric cancer liver metastasis who were treated by different modalities: a nationwide, multicenter clinical study
Li LI ; Yunhe GAO ; Liang SHANG ; Zhaoqing TANG ; Kan XUE ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Bin KE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Hongqing XI ; Yun TANG ; Zhi QIAO ; Han LIANG ; Jiafu JI ; Lin CHEN
Chinese Journal of Digestive Surgery 2024;23(1):114-124
		                        		
		                        			
		                        			Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.
		                        		
		                        		
		                        		
		                        	
6.Therapeutic effect and mechanism of piracetam for the treatment of spinal cord injury in rats through MAPK path-way
Bo DONG ; Yue LI ; Ying-Chun LI ; Tong WANG ; Zhuang LIANG ; Xi-Jing HE
China Journal of Orthopaedics and Traumatology 2024;37(6):591-598
		                        		
		                        			
		                        			Objective To explore mechanism of piracetam for the treatment of spinal cord injury in rats through mitogen-activated protein kinase(MAPK)pathway.Methods Fifty-four healthy 6-week-old SD female rats with body weight of 80 to 100 g were divided into sham operation group,spinal cord injury group and piracetam group by random number table method,with 18 rats in each group.Spinal cord injury model was established in spinal cord injury group and piracetam group using percussion apparatus,while sham operation group did not damage spinal cord.Piracetam group was injected with pirac-etam injection through tail vein according to 5 ml·kg-1 standard,once a day for 3 days;the other two groups were injected with normal saline at the same dose,the same frequency and the same duration.The rats were sacrificed at 1,3,and 7 days after surgery,and changes of Basso,Beattie and Bresnahan(BBB)locomotor rating scale was observed and compared.Enzyme-linked immunosorbent assay(ELISA)was used to detect spinal cord inflammatory factors,such as interleukin-6(IL-6),in-terleukin-10(IL-10),interleukin-1β(interleukin-1β),necrosis factor-α(IL-1β)and tumor necrosis factor-α(TNF-α);HE staining was used to observe morphological changes of rats with spinal cord injury,and immunohistochemistry was used to observe expression level of aquaporin 4(AQP4).The activation of MAPK signaling pathway in spinal cord of rats after spinal cord injury was observed by western blotting(WB).Results BBB scores of sham operation group on 1,3 and 7 day were 21 points.In spinal cord injury group,the scores were(1±1),(4±1)and(7±2);piracetam group was(1±1),(5±1),(9±2),re-spectively;the difference between spinal cord injury group and sham operation group was statistically significant(P<0.05).HE staining showed that no abnormality was found in sham operation group.In spinal cord injury group,bleeding and degeneration of spinal cord tissue appeared at 1 day after operation;flaky necrotic areas were appeared in spinal cord at 3 days after surgery,and spinal cord tissue began to slowly repair at 7 days after surgery.In piracetam group,the bleeding area was less than that of spinal cord injury group at 1 day after surgery;at 3 days after operation,the necrotic area was reduced and the range of nuclear disappearance was reduced;and the spinal cord began to recover slowly at 7 days after surgery.AQP4 staining of spinal cord of rats in sham operation group was weak at 1,3 and 7 days after modeling,AQP4 staining was deepened and area increased in spinal cord injury group,AQP4 staining of piracetam group was lighter than that of spinal cord injury group,and the positive cells were slightly increased and the staining was slightly darker than that of sham operation group.At 1,3 and 7 days,the level of IL-6,IL-10,IL-1β and TNF-α in spinal cord injury group were higher than those in sham operation group and piracetam group(P<0.05).Compared with spinal cord injury group,the area of spinal cord bleeding and necrosis were de-creased by HE staining in piracetam group,and AQP4 staining was decreased by immunohistochemistry.WB results showed that P-ERK,P-JNK and P-P38 levels in spinal cord injury group at 3 days were higher than those in sham operation group and piracetam group(P<0.05).Conclusion Piracetam not only showed significant effect in promoting motor function recovery after spinal cord injury,but also showed positive therapeutic potential in reducing lesion area,regulating AQP4 expression to reduce edema,and reducing inflammatory response by regulating MAPK signaling pathway.
		                        		
		                        		
		                        		
		                        	
7.Structure-activity Omics on Anti-inflammatory and Analgesic Effect of Bupleuri Radix in Qizhi Weitong Granules
Xi LUO ; Bing QI ; Ying MENG ; Xinpeng QIN ; Yongrui BAO ; Tianjiao LI ; Liang WANG ; Shuai WANG ; Xiansheng MENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):146-153
		                        		
		                        			
		                        			ObjectiveTo identify the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Bupleuri Radix by structure-activity omics. MethodA mouse model of pain was established with formaldehyde to examine the anti-inflammatory and analgesic effects of saikosaponins in vivo. The core targets of the active components in Bupleurum Radix for the anti-inflammatory and analgesic effects were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Online Mendelian Inheritance in Man (OMIM), and Search Tool for Recurring Instances of Neighbouring Genes (STRING). The key core targets with high binding affinity were screened based on the comprehensive score in the molecular docking between different types of saikosaponins and core targets. The structure-activity relationship was discussed and analyzed based on the binding of compounds to pharmacodynamic targets. ResultSaikosaponins alleviated the foot swelling induced by formaldehyde and reduced the content of prostaglandin E2 (PGE2) in the mouse model, showcasing a significant inhibitory effect on the inflammatory pain caused by PGE2. Nine components and 39 targets of saikosaponins, as well as 3 074 targets of anti-inflammatory and analgesic effects were screened out, and 22 common targets shared by saikosaponins and the effects were obtained as the direct targets. The protein-protein interaction (PPI) analysis showed that the main active components of Bupleurum Radix were saikosaponins a, b1, b2, b3, c, d, e, f, and v, and the key targets were fms-related receptor tyrosine kinase 1 (FLT1), kinase insert domain receptor (KDR), fibroblast growth factor 2 (FGF2), vascular endothelial growth factor A (VEGFA), and signal transducer and activator of transcription 3 (STAT3). Molecular docking between saikosaponins and the top 5 targets with high degrees in PPI network analysis revealed 25 highly active docks, including 6 docks with scores of 5-6 and 18 docks with scores above 6. ConclusionThis study adopted structural-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Bupleuri Radix in vivo, providing new ideas and methods for identifying the pharmacodynamic substances in traditional Chinese medicine. 
		                        		
		                        		
		                        		
		                        	
8.Biological characteristics of induction-produced polyploid tumor giant cells in ovarian cancer cell line SKOV3
Aiqi QIAO ; Xiaoyan YAN ; Gang LIANG ; Yanfeng XI ; Lingmin LI
Cancer Research and Clinic 2024;36(3):199-204
		                        		
		                        			
		                        			Objective:To investigate the morphological and biological characteristics of polyploid tumor giant cells (PGCC) produced by ovarian cancer cell line SKOV3 induced by CoCl 2. Methods:Human ovarian cancer cell line SKOV3 was induced-cultured with 300 μmol/L CoCl 2 in the simulated hypoxic environment for 36 h, the live cells continued to be conventionally cultured and passaged, and the cells collected 20 days later were PGCC group; SKOV3 cell line cultured conventionally was the control group. The formation process and morphological characteristics of PGCC were observed by inverted microscope. The expression of tumor stem cell markers OCT4 and CD117 were detected by immunocytochemistry. The adipogenic differentiation and osteogenic differentiation potential of PGCC were detected by using human bone marrow mesenchymal stem cell adipogenic differentiation assay kit and human bone marrow mesenchymal stem cell osteogenic differentiation assay kit.The cell migration ability of PGCC was detected by scratch assay. PGCC group and control group SKOV3 cells were treated with 1 μmol/L paclitaxel, and the cell morphology of the two groups was observed by microscope at 0, 24 and 48 h to detect the resistance of PGCC to chemotherapy drugs. Results:A small amount of PGCC was observed in SKOV3 cell line cultured in conventional medium under the microscope. CoCl 2 can induce SKOV3 cells to form PGCC, which was nearly round in shape and lacked branching. Its volume was 3 times or more than that of SKOV3 cells, and the nuclei were usually megakaryons or multinucleates, PGCC can produce daughter cells by budding. Immunocytochemical staining showed that OCT4 was positive in some PGCC, but no CD117 was positive. Neither OCT4 nor CD117 was expressed in SKOV3 cells. When cultured with lipid-induced differentiation medium of human bone marrow mesenchymal stem cells, the formation of large vacuoles in the cytoplasm of PGCC was observed at the 3rd cycle, and orange-red, round-like lipid droplets were shown by oil red O staining. Human bone marrow mesenchymal stem cells were cultured in osteogenic induction culture medium for 20 days, and alizarin red staining showed that calcium nodules formed significantly in cells of PGCC group compared with the control group. The cell scratch assay results showed that the migration rates of PGCC cultured in serum-free medium [(59±1)%, (66±3)%] were higher than those of the control group [(11±3)%, (14±5)%] at 24 and 48 h after scratch ( t values were 32.20 and 19.55, both P < 0.001). The migration rates of PGCC cultured in 10% serum medium [(92±3)%, (100±0)%] were higher than those of the control group [(20±6)%, (59±9)%] ( t values were 16.19 and 8.00, both P < 0.001). After 1 μmol/L paclitaxel treatment for 48 h, most of the cells in the PGCC group still survived, while most of the SKOV3 cells in the control group died. Conclusions:PGCC produces daughter cells by budding. PGCC has the characteristics of tumor stem cells: it expresses tumor stem cell markers and has the potential for multidirectional differentiation and strong resistance to chemotherapy drugs.
		                        		
		                        		
		                        		
		                        	
9.Effects of Bimin Formula (鼻敏方) on the Nasal Mucosa TMEM16A/NF-κB/MUC5AC Signaling Pathway in a Rat Model of Allergic Rhinitis with Lung-Spleen Qi Deficiency
Ningcong XU ; Yiwei HUA ; Xi TAN ; Jinhan WANG ; Zihua LIANG ; Shiqing ZHOU ; Yunying LI ; Wenyong CHEN ; Jiyan XIA ; Qiulan LUO
Journal of Traditional Chinese Medicine 2024;65(8):842-848
		                        		
		                        			
		                        			ObjectiveTo explore the possible mechanism of Bimin Formula (鼻敏方) in treating lung-spleen qi deficiency syndrome of allergic rhinitis (AR) with high mucin secretion. MethodsThirty-four SD rats were randomly divided into a blank group (8 rats), a model group (8 rats), a low-dose Bimin Formula group (8 rats), and a high-dose Bimin Formula group (10 rats). Except for the blank group, the other groups were subjected to AR lung-spleen qi deficiency rat models induced by smoking, gavage of Ginkgo biloba leaf extract, and ovalbumin. After modeling, rats in the low- and high-dose Bimin Formula groups were given Bimin Formula concentrate (concentration of 2.16 g/ml) by gavage at doses of 1.08 g/100 g and 2.16 g/100 g, respectively, while rats in the model group were given 0.5 ml/100 g of normal saline by gavage, once daily for 28 days; the blank group was not intervened. Behavioral assessments were performed after intervention. ELISA was used to detect the levels of peripheral blood total immunoglobulin E (IgE). HE staining was used to observe the pathological changes of nasal mucosa epithelium in rats, while immunohistochemistry was used to detect the expression of transmembrane protein 16A (TMEM16A) and mucin 5AC (MUC5AC) protein in nasal mucosa. Western Blot was used to detect the expression of nuclear factor kappa B (NF-κB) protein, and RT-PCR was used to detect the expression of TMEM16A, MUC5AC, and NF-κB mRNA in nasal mucosa. ResultsHE staining showed that the nasal mucosa epithelial cell structure in the blank group was intact without shedding, swelling, or necrosis; the nasal mucosa epithelial tissue of rats in the model group was thickened and partially shed, with infiltration of eosinophils and lymphocytes visible; the pathological changes in nasal mucosa tissue of rats in the high- and low-dose Bimin Formulagroups were improved, and more improvement was showen in the high-dose group. Compared with those in the blank group, the behavioral scores and peripheral blood total IgE levels of rats in the model group significantly increased, as well as the expression of TMEM16A, MUC5AC, and NF-κB proteins and mRNA in nasal mucosa (P<0.05 or P<0.01). Compared with those in the model group, the behavioral scores and peripheral blood total IgE levels of rats in the high-dose Bimin Formula group decreased, and the expression of TMEM16A, MUC5AC, and NF-κB proteins and mRNA in nasal mucosaalso decreased (P<0.05 or P<0.01); the behavioral scores and peripheral blood total IgE levels of rats in the low-dose Bimin Formula group were reduced, and the expression of TMEM16A and MUC5AC proteins and mRNA in nasal mucosa, as well as the expression of NF-κB protein decreased (P<0.05 or P<0.01), but the difference in NF-κB mRNA expression was not statistically significant (P>0.05). Compared with the low-dose Bimin Formula group, the expression of NF-κB protein in the high-dose group decreased (P<0.01). ConclusionBimin Formula may improve the symptoms and high mucus secretion of AR lung-spleen qi deficiency by regulating the TMEM16A/NF-κB/MUC5AC signaling pathway in nasalmucosa. 
		                        		
		                        		
		                        		
		                        	
10.Structure-activity Omics on Anti-inflammatory and Analgesic Effect of Cyperi Rhizoma in Qizhi Weitong Granules
Ying ZHENG ; Sicong LIU ; Xi LUO ; Bing QI ; Shuai WANG ; Yongrui BAO ; Tianjiao LI ; Liang WANG ; Dong YAO ; Xiansheng MENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):153-160
		                        		
		                        			
		                        			ObjectiveTo elucidate the pharmacodynamic substances responsible for the anti-inflammatory and analgesic effects of Cyperi Rhizoma by structure-activity omics. MethodOn the basis of the previous in vitro efficacy study by our research group, this study explored the in vivo efficacy of the flavonoids in Cyperi Rhizoma. The flavonoids in Cyperi Rhizoma and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PharmMapper, Swiss TargetPrediction, and available articles. The targets of the anti-inflammatory and analgesic effects were collected from DisGeNET and Online Mendelian Inheritance in Man (OMIM). The common targets shared by flavonoids and the effects were selected as the direct targets of flavonoids endowing Cyperi Rhizoma with anti-inflammatory and analgesic effects, and protein-protein interaction (PPI) network of the core targets was constructed. The method of structure-activity omics was employed to correlate the structure and efficacy of one or more classes of chemical components in Cyperi Rhizoma with the targets as a bridge. The components were classified according to structure. Molecular docking of components to core targets was carried out via SYBYL-X 2.1.1, PyMol, and Discovery Studio 4.5 visualizer. Two targets with the highest binding affinity were selected to explore the relationship between compound structures and targets. ResultThe flavonoids in Cyperi Rhizoma exerted anti-inflammatory and analgesic effects on the mouse model of pain induced by formaldehyde. Eighteen components and 115 direct targets were screened out, and the core targets with high activities were protein kinase B1 (Akt1), interleukin-1β (IL-1β), cellular tumor antigen p53 (TP53), prostaglandin-endoperoxide synthase 2 (PTGS2), and matrix metalloproteinase-9 (MMP-9). According to the structures, the flavonoids in Cyperi Rhizoma were classified into bioflavonoids, flavonols, flavones, and flavanes. The molecular docking results showed that flavonoids of Cyperi Rhizoma had the highest binding affinity to TP53 and PTGS2. The results of structure-activity omics showed that bioflavonoids represented the best binding structure to the targets, while their polyhydroxyl etherification resulted in a significant decrease in the binding affinity to PTGS2. Glycosides had higher binding affinity to PTGS2. The introduction of the long-chain hydrocarbon group to the A ring of flavonols facilitated the binding to TP53, while the change of B ring substituents was not the main factor affecting the binding affinity. The 3,4-dihydroxyl flavane outperformed 3-hydroxyl flavane in the binding to TP53, while the two compounds showed similar binding affinity to PTGS2. ConclusionThe method of structure-activity omics was used to analyze the material basis for the anti-inflammatory and analgesic effects of flavonoids in Cyperi Rhizoma. Structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine. 
		                        		
		                        		
		                        		
		                        	
            

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