1.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. 
		                        		
		                        		
		                        		
		                        	
2.The role of glucose metabolism reprogramming and its targeted therapeutic agents in inflammation-related diseases
Yi WEI ; Xiao-man JIANG ; Shi-lin XIA ; Jing XU ; Ya LI ; Ran DENG ; Yan WANG ; Hong WU
Acta Pharmaceutica Sinica 2024;59(3):511-519
		                        		
		                        			
		                        			 Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases. 
		                        		
		                        		
		                        		
		                        	
3.Epidemiological Investigation of Dampness Syndrome Manifestations in the Population at Risk of Cerebrovascular Disease
Xiao-Jia NI ; Hai-Yan HUANG ; Qing SU ; Yao XU ; Ling-Ling LIU ; Zhuo-Ran KUANG ; Yi-Hang LI ; Yi-Kai ZHANG ; Miao-Miao MENG ; Yi-Xin GUO ; Xiao-Bo YANG ; Ye-Feng CAI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):531-539
		                        		
		                        			
		                        			Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.
		                        		
		                        		
		                        		
		                        	
4.Nutrition-related influencing factors of myopia among adolescents in Zhengding County, Shijiazhuang City
Yi YOU ; Fangfang LIU ; Hongyu QIN ; Lamei XU ; Ran JING ; Shuqing GAO
Chinese Journal of Child Health Care 2024;32(4):395-400
		                        		
		                        			
		                        			【Objective】 To analyze nutrition-related factors that affect the prevalence of myopia in adolescents, in order to provide reference for primary prevention of myopia. 【Methods】 A stratified sampling method was used to select 385 adolescents from Zhengding County in October 2021. Adolescents in this study took vision testing, physical examination and completed a questionnaire survey. One-way analysis of variance and lasso regression were used to screen the variables, and Logistic regression was used to determine the possible influencing factors of myopia. Factor analysis was adopted to extract the dietary patterns of adolescents in Zhengding County, then the association between dietary patterns and myopia was analyzed. 【Results】 A total of 385 adolescents were surveyed, with the prevalence rate of myopia of about 68.6%. Multivariate analysis revealed that fried food(OR=8.480, 95%CI:1.058 - 67.971) was a risk factor for myopia, while intake of milk and dairy products(OR=0.994, 95%CI:0.991 - 0.999), soybeans and nuts(OR=0.997, 95%CI:0.994 - 0.999), no myopia in either parent(OR=0.312, 95%CI:0.115 - 0.845), physical education class 4 times per week(OR=0.269, 95%CI:0.074 - 0.984) were statistically associated with a lower risk of myopia(P<0.05). Three dietary patterns was extracted through factor analysis, including diversified dietary pattern, soy-hybrid dietary pattern, and snack and beverage dietary pattern. Logistic analysis results indicated that soy-hybrid dietary pattern(OR=0.85, 95%CI:0.73 - 0.99,P<0.05) was statistically associated with myopia. 【Conclusions】 The problem of myopia among adolescents in Zhengding County is more serious. Increasing the intake of milk and dairy products, soybeans and nuts, reducing the intake of fried foods, and adjusting the overall dietary structure should be recommended in order to prevent the development of myopia in adolescents.
		                        		
		                        		
		                        		
		                        	
5.Status of parent-child bed sharing and its influences on children
Min XU ; Yanchun SHAN ; Ni RAN ; Zhaochuan YANG ; Mingji YI
Chinese Journal of Child Health Care 2024;32(3):312-316
		                        		
		                        			
		                        			The influence of bed sharing on children′s physical and psychological health has been concerned as one of the main types of sleep arrangements.At present, there are significant differences in bed sharing among children of different ages, groups, regions and races.There are also studies on the impact of bed sharing sleep on children′s health, on the one hand, it is conducive to breastfeeding, where infants get enough security; on the other hand, it leads to an increase in the incidence of sudden infant death syndrome, and an increase in the number of night awakenings.Therefore, it is important to understand the current research situation of bed sharing and its influences on children, thus to better promote children healthy growth.
		                        		
		                        		
		                        		
		                        	
6.Immunotherapy for Colorectal Cancer
Hao-Ran XU ; Xiao-Yi ZHAO ; He NIE ; Hui WANG ; Qing-Lin ZHANG ; Qiang ZHAN
Progress in Biochemistry and Biophysics 2024;51(10):2570-2586
		                        		
		                        			
		                        			Improving the prognosis of patients with colorectal cancer (CRC) holds important clinical and social significance. Immunotherapy is an emerging therapy approach for cancers, which mainly include immune checkpoint inhibitors (ICI), immune vaccine and adoptive cell therapy. ICI have achieved good clinical translation in treatment of metastatic CRC with deficient DNA mismatch repair/high microsatellite instability (dMMR/MSI-H) status. The application of some ICI, such as PD-1 inhibitors pembrolizumab and nivolumab, in this type patients have been approved by the FDA. In addition,numerous positive results are acquired in clinical trials of neoadjuvant therapy for resectable dMMR/MSI-H CRC. These results greatly bolstered the exploration enthusiasm of CRC immunotherapy. However, the proficient DNA mismatch repair/microsatellite stability (pMMR/MSS) CRC, which accounting for the vast majority in related patients, hardly benefit from ICI therapy. Various combination strategies, mainly including ICI combined with traditional chemotherapy, radiotherapy, or targeted therapy, have been attempted to alter the “cold tumors” microenvironment characteristics of pMMR/MSS CRC in clinical trials, whereas no breakthrough results were reached. Theoretically, tumor vaccines are ideal choice to break down the barrier of insufficient immune infiltration in solid tumors. However, the outcomes of related clinical trials in CRC patents are not satisfactory, and partially due to the weak specificity of the applied tumor-associated antigens. Clinical studies of adoptive cell therapy in CRC are also actively underway. The favorable efficacy of tumor-infiltrating lymphocyte, cytokine-induced killer (CIK) and dendritic cell-CIK in CRC have been confirmed, while the CAR-T and TCR-T therapies need more exploration based on screening more suitable antigens and optimizing engineering design. In this review, we made a summary based on the mainline of clinical studies related to diverse immunotherapies, so as to clarify the progress of CRC immunotherapy and provide bases for exploration of better treatment options. 
		                        		
		                        		
		                        		
		                        	
7.Effects of electroacupuncture at"Zusanli"and"Taichong"on gastrointestinal function and brain-gut axis in model rats with functional dyspepsia
Qiong WANG ; Yi ZHANG ; Ran ZOU ; Li ZHOU ; Min YANG ; Paidi XU
Journal of Beijing University of Traditional Chinese Medicine 2024;47(4):570-579
		                        		
		                        			
		                        			Objective We aimed to investigate the effects of electroacupuncture at"Zusanli"(ST36)and"Taichong"(LR3)on gastrointestinal motility,gastrointestinal hormones,and brain-gut axis in rats with functional dyspepsia(FD).Methods 48 SD rats were randomly divided into a normal control group,a model group,a cisapride group,and an electroacupuncture group,with 12 rats in each group.A mild tail pinch stimulation combined with intermittent food deprivation was used to establish the FD rat model.Body mass,food intake,and sucrose preference rate were recorded before and after modeling to verify the success of the FD model.After modeling,the normal control group and the model group received no intervention;the cisapride group rats were administered cisapride[0.4 g/(kg·d)]by intragastric perfusion for 6 consecutive days as one course of treatment,with a rest day between each course;the electroacupuncture group rats received electroacupuncture stimulation at bilateral"Zusanli"and"Taichong"(DC,dense-sparse wave,2/100 Hz,2-5 mA.Electricity was applied for 30 min),with stimulation every 24 h for 6 consecutive times as one course of treatment,with a rest day between each course.After two courses of treatment,samples were collected to compare gastrointestinal motility indices,blood levels of gastrointestinal hormones[motilin,gastrin,serotonin(5-HT),nitric oxide(NO)],serum and tissue levels of endogenous brain-gut peptides[cholecystokinin(CCK),calcitonin gene-related peptide(CGRP),neuropeptide Y(NPY)]in the hypothalamus,gastric antrum,duodenum,colon,and protein expressions of ghrelin and substance P in the hypothalamus,spinal cord,gastric antrum,and colon.Results Body mass,food intake,and sucrose preference rate were lower of the model rats than those of the normal rats(P<0.05).Compared with the model group,rats in the electroacupuncture group and cisapride group had(i)lower gastric residual rates,higher rates of small intestinal propulsion and gastric slow wave main frequency and power(P<0.05);(ii)levels of motilin,gastrin,and 5-HT increased,while NO level decreased(P<0.05);(iii)serum CCK content increased,while CGRP and NPY levels decreased(P<0.05);(iv)CCK protein positive expression increased,while CGRP and NPY protein positive expression decreased in the hypothalamus,gastric antrum,duodenum(P<0.05);(v)ghrelin protein expressions increased,and substance P protein expression decreased in the hypothalamus,spinal cord,gastric antrum,and colon(P<0.05).There were no significant differences in these indicators between the electroacupuncture group and the cisapride group.Conclusion Electroacupuncture at"Zusanli"and"Taichong"can effectively alleviate gastrointestinal motility disorders in FD rats,regulate gastrointestinal hormone levels,reverse abnormal brain-gut peptide expression,and regulate brain-gut interaction balance.
		                        		
		                        		
		                        		
		                        	
8.Research Progress in the Differentiation and Treatment of Precancerous Lesions of Gastric Cancer with Traditional Chinese Medicine in Recent 10 Years
Si-Zhong XU ; Jia-Qi LIU ; Yun-Ran LI ; Yi ZHAO
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(8):2219-2224
		                        		
		                        			
		                        			This paper reviewed the research progress in the differentiation and treatment of precancerous lesions of gastric cancer(PLGC)with traditional Chinese medicine(TCM)in the recent 10 years.PLGC refers to the intestinal metaplasia and dysplasia of gastric mucosa developed from chronic atrophic gastritis.As an intermediate stage between chronic atrophic gastritis and gastric cancer,PLGC progresses slowly.TCM has certain advantages in the treatment of PLGC.PLGC can be mainly differentiated as five TCM syndrome types:spleen-stomach weakness syndrome,damp-heat in the spleen and stomach syndrome,qi stagnation in the liver and stomach syndrome,stasis obstruction in the stomach collateral syndrome,and stomach-yin deficiency syndrome.The popularization of gastroscopy technology has promoted the development of microscopic syndrome differentiation of gastric diseases.The combination of microscopic syndrome differentiation and macroscopic syndrome differentiation provides more theoretical supports for the TCM syndrome differentiation and treatment of PLGC.The basic pathogenesis of PLGC is due to the weakness of spleen and stomach and the disordered qi movement in the spleen and stomach,complicated by the accumulation of pathological factors such as damp-heat,stasis-toxin,phlegm-damp,and then the stomach-yin will be consumed over time.An amount of clinical studies on the treatment of PLGC with Chinese medicine have been carried out in recent years.The Chinese medicine treatment of PLGC is mainly through benefiting qi and invigorating spleen,assisted by the methods of soothing liver and activating blood,resolving dampness and eliminating stasis,resolving stasis and removing toxins,and nourishing yin and benefiting stomach,so as to prevent the PLGC progressing to gastric cancer.There are few studies on acupuncture treatment of precancerous lesions of gastric cancer.Therefore,it is necessary to carry out more strict and standardized multi-center large-sample RCTs,and to further study the therapeutic mechanism of acupuncture and moxibustion for PLGC,in order to provide more high-level evidence for the treatment of PLGC with TCM therapy.
		                        		
		                        		
		                        		
		                        	
9.Locking compression plating for treatment of periprosthetic distal femur fractures in the aged
Yake LIU ; Zhenyu ZHOU ; Ran TAO ; Yi CAO ; Jianwei ZHU ; Youhua WANG ; Yue LU ; Hua XU ; Jiacheng XU ; Hongdong MA ; Jining SHEN ; Fengxiang ZHAO ; Kefan WU ; Fan LIU
Chinese Journal of Orthopaedic Trauma 2024;26(9):790-796
		                        		
		                        			
		                        			Objective:To explore the clinical outcomes of locking compression plating (LCP) in the treatment of periprosthetic fracture (PPF) of the distal femur in the aged patients.Methods:A retrospective study was performed to analyze the 31 aged patients who had been treated at Department of Orthopedic Surgery, The Affiliated Hospital to Nantong University for PPF of the distal femur with LCP between June 2012 and May 2023. There were 27 females and 4 males with an age of (80.2±6.1) years. According to the Unified Classification System (UCS), 18 PPFs were classified as type Ⅴ.3B1 and 6 PPFs as type Ⅴ.3B2 after total knee arthroplasty and 7 PPFs as type Ⅳ.3C after total hip arthroplasty. The patients were fixated with a lateral single plate in 25 cases, and with lateral and medial dual plates in 6 cases. The surgical time, intraoperative blood loss, hospitalization time, postoperative weight-bearing time, fracture healing time, and knee joint function and complications during follow-up were recorded.Results:For the 25 patients undergoing fixation with a lateral single plate, the surgical time was (58.7±7.9) minutes, the intraoperative blood loss (78.0±15.1) mL, the hospitalization time (6.9±1.6) days, the postoperative weight-bearing time (5.9±1.4) days, and the follow-up time 37 (15, 51) months. For the 6 patients undergoing fixation with lateral and medial dual plates, the surgical time was (186.6±9.8) minutes, the intraoperative blood loss (1,256.7±231.2) mL, the hospitalization time (17.8±3.3) days, the postoperative weight-bearing time (3.6±0.6) days, and the follow-up time 17 (16, 21) months. The fracture healing time was (14.9±2.0) and (18.7±2.6) weeks, respectively, for patients fixed with single and double steel plates. By the scoring criteria of the American Hospital for Special Surgery (HSS), the knee joint function was evaluated at the last follow-up as excellent in 10 cases and as good in 15 cases for the 25 patients undergoing fixation with a lateral single plate, and as good for all the 6 patients undergoing fixation with lateral and medial dual plates. No patient experienced such complications as incision infection, bone nonunion, or internal fixation failure during the follow-up period.Conclusions:LCP fixation can achieve satisfactory outcomes in the treatment of PPF of the distal femur in the aged patients. As fixation with a single lateral femoral plate is suitable for most of the aged patients with PPF of the distal femur, it can be used as the first choice. Fixation with dual plates can provide stronger stability, but its indications should be strictly controlled.
		                        		
		                        		
		                        		
		                        	
10.Research progress on ferroptosis regulated by glycolysis-fatty acid metabolism in metabolic diseases
Xiao-man JIANG ; Ran DENG ; Yi WEI ; Shi-lin XIA ; Jing XU ; Ya LI ; Hong WU
Acta Pharmaceutica Sinica 2023;58(5):1204-1210
		                        		
		                        			
		                        			 In metabolic diseases, the accumulation of reactive oxygen species and oxidative stress are closely associated with ferroptosis. As a key regulatory factor, the imbalance between glycolysis and fatty acid metabolism can participate in ferroptosis directly or indirectly, thereby regulating the occurrence and development of various metabolic diseases. The essence of ferroptosis is a new regulatory cell death mode, which is caused by the excessive accumulation of iron-dependent lipid peroxide. It is closely related to glycolysis and fatty acid metabolism, which plays an important role in metabolic diseases. This regulatory cell death mode is significantly distinguished from other programmed cell death modes and has unique changes in cell morphology, symbolic characteristics and mechanisms. This paper first illustrates the main mechanism of glycolysis and fatty acid metabolism imbalance in the occurrence of ferroptosis, then reviews the research progress of ferroptosis in tumor, diabetes, rheumatoid arthritis and other metabolic diseases, and finally reveals the internal connection between glycolysis-fatty acid metabolism imbalance and ferroptosis, as well as its impacts on metabolic diseases, which provide new strategies for the prevention and treatment of metabolic diseases. 
		                        		
		                        		
		                        		
		                        	
            
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