1.Preclinical and clinical studies on Qin-Zhu-Liang-Xue decoction: insights from network pharmacology and implications for atopic dermatitis treatment.
Keke HUANG ; Qingkai LIU ; Ruoxi ZHANG ; Hua NIAN ; Ying LUO ; Yue LUO ; Xiaoya FEI ; Le KUAI ; Bin LI ; Yimei TAN ; Su LI ; Xin MA
Frontiers of Medicine 2025;19(1):134-148
To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy*
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Animals
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Drugs, Chinese Herbal/administration & dosage*
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Humans
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Mice
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Network Pharmacology
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Male
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Female
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Adult
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Receptors, Glucocorticoid/metabolism*
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Disease Models, Animal
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Single-Blind Method
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Middle Aged
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Young Adult
2.Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation.
Hang ZHAO ; Xin MA ; Hao WANG ; Xiao-Jie DING ; Le KUAI ; Jian-Kun SONG ; Zhan ZHANG ; Dan YANG ; Chun-Jie GAO ; Bin LI ; Mi ZHOU
Journal of Integrative Medicine 2025;23(3):309-319
OBJECTIVE:
To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD).
METHODS:
The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4+ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis.
RESULTS:
POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA.
CONCLUSION
Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy*
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Animals
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Humans
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Cell Differentiation/drug effects*
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Phosphorylation/drug effects*
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Mice
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Th2 Cells/drug effects*
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Keratinocytes/drug effects*
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Disease Models, Animal
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Mice, Inbred BALB C
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Calcitriol/analogs & derivatives*
3.An update on the role of long non-coding RNAs in psoriasis.
Jian-Kun SONG ; Shuang-Yi YIN ; Wei LI ; Xiao-Dong LI ; Yue LUO ; Ying LUO ; Meng XING ; Bin LI ; Le KUAI
Chinese Medical Journal 2020;134(4):379-389
Increasing evidence suggests that long non-coding RNAs (lncRNAs) are of vital importance for various biological processes, and dysregulation of lncRNAs is frequently associated with various diseases such as psoriasis. LncRNAs modulate gene expression at the transcriptional, post-transcriptional, and translational levels; however, the specific regulatory mechanisms of lncRNAs in psoriasis remain largely unexplored. This review provides an overview of recent studies investigating mechanisms and functions of lncRNAs in psoriasis, especially focusing on the role of lncRNAs in keratinocytes, T cells, and dendritic cells.
Humans
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Psoriasis/genetics*
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RNA, Long Noncoding/genetics*
4.Application and study on blended learning in practical training of acupuncture techniques
Fan WANG ; Huaijin CHENG ; Xiaojie SU ; Jianmin XU ; Tingting ZHANG ; Kangmin TANG ; Le KUAI
Chinese Journal of Medical Education Research 2019;18(2):126-130
Objective To explore the effect of blended learning in practical training of acupuncture techniques.Methods Sophomores of acupuncture and Tuinaspeciality were divided into two groups based on classes,with 38 students in experimental group and 34 in control group,adopting blended learning and traditional method in teaching acupuncture techniques respectively.Blended learning mainly adopts mixed methods of both online "punch-card" on WeChat community and offline class learning.Post-test score of two groups were compared by independent samples t-test with SPSS 19.0.The teaching effect of blended learning was evaluated in students in experimental group by questionnaire survey.Results The total score of acupuncture techniques (4.73 ± 0.15) in experimental group were significantly higher than that of control group (4.27 ± 0.46) (t=5.588,P<0.01) and students' satisfaction concerning the blended learning in experimental group was up to 88% (22/25).Conclusion Blended learning can promote students' acupuncture skills and cultivate good study habits,making practice in class more targeted.More friendly online learning tools needs to be further developed.
5.Establishment of an Examination and Assessment System of Filiform Needle Manipulation
Tingting ZHANG ; Caihong WANG ; Le KUAI ; Fan WANG ; Jianmin XU
Shanghai Journal of Acupuncture and Moxibustion 2017;36(7):876-880
Filiform needle acupuncture technique is the core content of needling and moxibustion method. The examination and assessment of filiform needle manipulation are the most important measure for testing the effect of filiform needle acupuncture technique teaching. The establishment of a scientific examination and assessment system of filiform needle manipulation should involve comprehensive examination and assessment contents, definite and detailed evaluation rules and quantified scoring criteria to make the examination and assessment system be able to comprehensively and objectively assess the students' skills of filiform needle manipulation to achieve the purpose of improving the quality of filiform needle acupuncture technique teaching.
6.Progress in research on the novel cancer therapeutic target Cdc20
Xiang-yang LE ; Meng-ni KUAI ; Qian-bin LI ; Zhuo CHEN
Acta Pharmaceutica Sinica 2017;52(9):1366-1371
The anaphase promoting complex (APC) regulates cell cycle progression by forming two functionally distinct E3 ubiquitin ligase complexes, APCCdc20 activated by cell division cycle protein 20 (Cdc20) and APCCdh1 activated by Cdc20 homologue 1 (Cdh1), respectively. Cdc20 and Cdh1 have different functions in the occurrence and development of the tumor. Cdc20 is a cancer promoter while Cdh1 suppresses tumorigenesis. Emerging evidence has begun to reveal that Cdc20 has positive functions in tumorigenesis, the overexpression of Cdc20 has been observed in many cancers. Currently, Cdc20 inhibitors, mostly non-specific inhibitors except apcin, not only block the combination between Cdc20 and APC, also block the combination between Cdh1 and APC, which leads to a poor selectivity. In this paper, the Cdc20 role in the development and process of cancers and its inhibitors are reviewed.
7.Study on flipped classroom in teaching of “auricular needling method”
Fan WANG ; Le KUAI ; Tingting ZHANG ; Jianmin XU ; Caihong WANG
Chinese Journal of Medical Education Research 2016;15(2):168-171
Objective To explore the effect of flipped classroom in teaching auricular needling method. Methods Sophomores of acupuncture and Tuina speciality were divided into two groups based on classes, with 33 students in experimental group and 30 in control group. In teaching auricular needling method, experimental group adopted flipped classroom by online resources and classroom activities, while control group adopted traditional classroom such as teaching, watching video, demonstration. Post-test score of two groups were compared by independent samples t-test. The teaching effect of flipped classroom was evaluated by questionnaire survey of students in experimental group. Results The total score of auricular needling (88.4±13.91), score of location (55.40±7.34), and score of application (32.00±10.31) in experi-mental group were significantly higher than those in con-trol group (71.48±15.93, 47.55±12.23 and 23.94± 11.97) (P<0.05). Students' satisfaction concerning the flipped classroom in experimental group was up to 90%. Conclusion Flipped classroom can be used in teaching auricular needling method, which can improve teaching quality and promote improvement of students' self-study and communication skills.
8.Expression of Six1 and Six4 in esophageal squamous cell carcinoma and their correlation with clinical prognosis.
Qiao WEI ; Wei-wei YU ; Kuai-le ZHAO ; Xiao-long FU ; Zheng-fei ZHU ; Guang-qi QIN ; Huan CHEN ; Zhuan-xu ZHANG ; Yan-zi GU ; Jia-qing XIANG ; Hai-quan CHEN ; Xiang DU ; Meng-hong SUN
Chinese Journal of Pathology 2013;42(7):446-450
OBJECTIVESix1 and Six4 are expressed in several tumors, and associated with tumor progress and poor prognosis. The aim of this study was to investigate the expression of Six1 and Six4 in esophageal squamous cell carcinoma (ESCC), and to evaluate their correlation with the clinicopathological factors and prognosis.
METHODSTissue microarray technology and immunohistochemical method (EnVision) were used to detect the expression of Six1 and Six4 in the tumor tissues and corresponding adjacent normal epithelium of esophagus from 292 ESCC patients.
RESULTSAmong the 292 ESCC patients, the positive rates of Six1 and Six4 protein expression in tumor tissues were 72.9% (213/292) and 56.2% (164/292), respectively, significantly higher than the expression rate of 33.2% (97/292) and 32.5% (95/292) in adjacent normal epithelium of esophagus (P < 0.05). Chi square test showed that the expression of Six1 protein was related to tumor size, depth of tumor invasion and patient survival status; higher Six4 protein expression level was related to poor differentiation and increased depth of invasion. Single factor Log-rank analysis revealed that gender, TNM stage, Six1 protein expression level were related to the overall survival of ESCC patients (P < 0.05), while the five-year survival rate was significantly higher in the Six1-negative group than the Six1-positive group [51.9% (41/79) vs. 43.7% (93/213)]. Multi-factor Cox proportional risk model analysis showed that TNM stage and positive expression of Six1 were independent prognostic factors for ESCC patients (P < 0.05).
CONCLUSIONSSix1 and Six4 are highly expressed in ESCC. Their expression levels are closely related to the progress and prognosis of ESCC. Over-expression of Six1 is related to poor prognosis in ESCC patients. Thus, Six1 could be used as an important prognostic indicator for ESCC patients.
Adult ; Aged ; Carcinoma, Squamous Cell ; metabolism ; pathology ; surgery ; Esophageal Neoplasms ; metabolism ; pathology ; surgery ; Female ; Follow-Up Studies ; Homeodomain Proteins ; metabolism ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Survival Rate ; Trans-Activators ; metabolism ; Tumor Burden
9.Application of direct observation of procedural skills (DOPS) in teaching acupuncture manip-ulation skills
Le KUAI ; Tingting ZHANG ; Jianmin XU ; Fan WANG ; Caihong WANG
Chinese Journal of Medical Education Research 2013;(11):1081-1084
Objective To explore the effect of direct observation of procedural skills (DOPS) in teaching acupuncture manipulation skills. Methods Sophomores of acupuncture and Tuina spe-ciality were divided into two groups based on their classes, 36 students in experimental group and 31 in control group. In experimental group, DOPS on filiform needling was done twice in the middle and at the end of the semester respectively. In control group, DOPS was done once at the end of semester. The final exam's DOPS score and satisfaction degree of teachers and students concerning the results of the assessment in two groups were compared by independent samples t-test. P<0.05 indicates signifi-cant differences. The teaching effect of DOPS was also evaluated by questionnaire survey of students in experimental group. Results The total score of DOPS (4.26 ±0.24), scores of needle insertion (4.18±0.42), and scores of reinforcing and reducing method (4.03±0.28) in experimental group were higher than those in control group ((4.14±0.25), (4.00±0.29) and (3.87±0.37), P<0.05). The teachers' satisfaction (8.38±0.51) and students' satisfaction (8.47±1.03) concerning the results of the assessment in experimental group were higher than those in control group ((8.05±0.78) and (7.94±1.15), P<0.05). More than 80% of students in experimental group supported the saying of‘DOPS promoting students' skills training and enhancing the ability of handwork ’ . Conclusions DOPS can be used as an effective teaching and examination method and can improve students' skills of acupuncture manipulation.
10.Study on dose-effect relationship of electroacupuncture with different current intensities alleviating tibial cancer pain and inhibition of expression of spinal GFAP in rats.
Le KUAI ; Hao CHEN ; Ting-Ting ZHANG ; Hua-Yuan YANG
Chinese Acupuncture & Moxibustion 2012;32(4):331-337
OBJECTIVETo observe the dose-effect relationship of electroacupuncture of different current intensities combined with Morphine of different dosage on alleviating the rats' tibial cancer pain, and explore the possible mechanism, which could provide the experiment basis for alleviating the tibial cancer pain by electroacupuncture combined with Morphine.
METHODSOne hundred female Wistar rats were randomly divided into a normal group, a model group and eight treatment groups, 10 cases in each group. The rats in the treatment groups were treated by combined therapies of electroacupuncture of different intensities with 2 Hz /100 Hz dense-disperse wave on "Jiaji"(EX-B 2)and different dosage Morphine in 2 factor 3 level conditions, once a day for 6 days. The pain thresholds were observed before the treatment and 0 min, 1 h, 2 h and 5 h after the first treatment as well as after 3 and 6 times of treatments. The glial fibrillary acidic protein (GFAP) expression was determined by immunohistochemical method.
RESULTSThe rats' pain thresholds were significantly increased with electroacupuncture of 2 mA and 1 mA (all P < 0.01) on the 0 min, 1 h and 2 h of the first treatment, between which there were no significant differences (all P > 0.05). The pain threshold was still increased by electroacupuncture of 2 mA on the 5 h of the treatment (P < 0.01), while that of 1 mA failed to take effect (P > 0.05). After 3 and 6 times of treatments, both electroacupuncture of 2 mA and 1 mA had the effect of increasing the pain threshold (all P < 0.01), and the effect of 2 mA was superior to that of 1 mA (P < 0.05), had the synergistic effect with 5 mg/(kg x d) Morphine (P < 0.05). After 6 times of treatments, both electroacupuncture of 2 mA and 1 mA could inhibit the expression of GFAP (both P < 0.01), and there was no significant difference between them (P > 0.05). Both of 5 mg/(kg x d) and 2.5 mg/(kg x d) of Morphine, however, didn't bring about inhibition effect (P > 0.05).
CONCLUSIONThere is a does-effect relationship on electroacupuncture of different current intensity for alleviating the tibial cancer pain in rats. The electroacupuncture with 2 mA, which is better than that with 1 mA, has the synergistic effect with 5 mg/(kg x d) of Morphine. The electroacupuncture can inhibit the expression of GFAP to cooperate with Morphine for the purpose of alleviating the rats' tibial cancer pain.
Animals ; Bone Neoplasms ; complications ; genetics ; metabolism ; Electroacupuncture ; instrumentation ; methods ; Female ; Gene Expression Regulation, Neoplastic ; Glial Fibrillary Acidic Protein ; genetics ; metabolism ; Humans ; Pain ; etiology ; genetics ; metabolism ; Pain Management ; instrumentation ; methods ; Rats ; Rats, Wistar ; Spine ; metabolism ; Tibia ; metabolism

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