1.Mechanism of Intervening with Diarrhea-predominant Irritable Bowel Syndrome in Rats with Spleen Deficiency by Xingpi Capsules Through Regulating 5-HT-RhoA/ROCK2 Pathway
Gang WANG ; Lingwen CUI ; Xiangning LIU ; Rongxin ZHU ; Mingyue HUANG ; Ying SUN ; Boyang JIAO ; Ran WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):60-69
ObjectiveTo investigate the efficacy of Xingpi capsules (XPC) in treating diarrhea-predominant irritable bowel syndrome (IBS-D) with spleen deficiency and elucidate its potential molecular mechanisms. MethodsA rat model of IBS-D with spleen deficiency was established by administering senna leaf in combination with restrained stress and swimming fatigue for 14 d. Ten specific pathogen free (SPF)-grade healthy rats were used as the normal control group. After successful modeling, SPF-grade rats were randomly divided into a model group, a pinaverium bromide group (1.5 mg·kg-1), and low- and high-dose XPC groups (0.135 and 0.54 g·kg-1), with 10 rats in each group. Rats in the normal control group and the model group were given distilled water by gavage, while the remaining groups were administered corresponding drug solutions by gavage once a day for 14 consecutive days. The rat body weights and fecal condition were observed every day, and the Bristol score was recorded. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 5-hydroxytryptamine (5-HT) in serum and colon tissue. Transmission electron microscopy was used to observe the microvilli and tight junctions in the colon. The integrity of the colonic barrier, intestinal motility, and expression of related pathway proteins were evaluated by hematoxylin-eosin (HE) staining, immunohistochemistry, and Western blot. ResultsCompared with those in the normal control group, rats in the model group showed a significantly decreased body weight and increased diarrhea rate, diarrhea grade, and Bristol score (P<0.01). HE staining revealed incomplete colonic mucosa in the model group, with evident congestion and edema observed. Electron microscopy results indicated decreased density and integrity of the colonic barrier, shedding and disappearance of microvilli, and significant widening of tight junctions. The expression levels of colonic tight junction proteins Occludin and Claudin-5 were downregulated (P<0.01), and the levels of 5-HT in serum and colon tissue were elevated (P<0.01). The small intestine propulsion rate significantly increased (P<0.01), and the expression of contractile proteins Ras homolog family member A (RhoA) and Rho-associated coiled-coil containing protein kinase 2 (ROCK2) in colon and phosphorylation of myosin light chain (MLC20) were upregulated (P<0.01). Compared with the model group, the treatment groups showed alleviated diarrhea, diarrhea-associated symptoms, and pathological manifestations of colon tissue to varying degrees. Specifically, high-dose XPC exhibited effectively relieved diarrhea, promoted recovery of colonic mucosal structure, significantly reduced congestion and edema, upregulated expression of Occludin and Claudin-5 (P<0.01), decreased levels of 5-HT in serum and colon tissue (P<0.05,P<0.01), significantly slowed small intestine propulsion rate (P<0.01), and significantly downregulated expression of contractile proteins RhoA and ROCK2 in colon and phosphorylation of MLC20 (P<0.05,P<0.01). ConclusionXPC effectively alleviates symptoms of spleen deficiency and diarrhea and regulates the secretion of brain-gut peptide. The characteristics of XPC are mainly manifested in alleviating IBS-D with spleen deficiency from the aspects of protecting intestinal mucosa and inhibiting smooth muscle contraction, and the mechanism is closely related to the regulation of the 5-HT-RhoA/ROCK2 pathway expression.
2.Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes.
Shuo ZHANG ; Hong-Jin LI ; Chun-Mei YANG ; Liu LIU ; Xiao-Ying SUN ; Jiao WANG ; Si-Ting CHEN ; Yi LU ; Man-Qi HU ; Ge YAN ; Ya-Qiong ZHOU ; Xiao MIAO ; Xin LI ; Bin LI
Chinese journal of integrative medicine 2024;30(3):222-229
OBJECTIVE:
To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.
METHODS:
Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.
RESULTS:
TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).
CONCLUSIONS
TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male
;
Animals
;
Mice
;
Tripterygium
;
Psoriasis/drug therapy*
;
Keratinocytes
;
Skin Diseases/metabolism*
;
Cytokines/metabolism*
;
Imiquimod/metabolism*
;
Dermatitis/pathology*
;
Disease Models, Animal
;
Mice, Inbred BALB C
;
Skin/metabolism*
3.Application value of single energy metal artifact reduction in the follow-up CT angiography after endovascular repair of abdominal aortic aneurysm combined with coil embolization
Ying ZHANG ; Chun ZHOU ; Cheng LIU ; Kai HOU
Chinese Journal of Clinical Medicine 2024;31(6):984-989
Objective To explore the application value of single energy metal artifact reduction technology (SEMAR) in the CTA follow-up of complex abdominal aortic aneurysm endovascular repair (EVAR) combined with coil embolization using 320-slice CT spiral scanning mode. Methods A retrospective analysis was conducted on the images of 14 patients with abdominal aortic aneurysm and 2 patients with internal iliac artery aneurysm who underwent abdominal CTA reexamination 30 days after EVAR combined with coil embolization at Zhongshan Hospital, Fudan University from August 2023 to February 2024. The original data were reconstructed using a hybrid iterative reconstruction algorithm (non-SEMAR group) and a combined reconstruction and SEMAR algorithm (SEMAR group), and the artifact index (AI), contrast-to-noise ratio (CNR), and subjective scores between the two groups were compared. Results The AI values of up, down, left, right around the spring coil and adjacent aortic cavity in the SEMAR group were lower than those in the non-SEMAR group (38.16±19.20 vs 89.29±30.93, 30.75±16.28 vs 82.62±28.01, 33.61±16.18 vs 74.90±26.28, 44.99±15.91 vs 87.72±33.70, and 24.49±12.58 vs 47.29±13.55; P<0.001), and the CNRs in the SEMAR group were higher than those in the non-SEMAR group (2.47±2.15 vs 1.01±0.74, 2.32±2.01 vs 0.72±0.50, 4.93±4.15 vs 1.38±0.79, 4.10±4.14 vs 1.56±1.18, and 19.91±11.01 vs 11.01±7.77; P<0.05). Compared with the non-SEMAR group, the subjective scores of image in the SEMAR group were higher (P<0.001). Conclusions SEMAR technology can significantly reduce the artifact of spring coil, improve the clarity of tumors, visceral arteries, stents, and internal leaks images, and has important clinical significance for follow-up after EVAR surgery.
4.Effects of vitexin on rats with chronic obstructive pulmonary disease
Li-Ying LAI ; Xiao-Jing LIU ; Cong-Yun LEI ; Xiu-Chun YE
The Chinese Journal of Clinical Pharmacology 2024;40(2):210-214
Objective To study the effect of vitexin inhibiting Ras homology C(RhoC)/Rho-associated kinase(ROCK)signaling on lung inflammation and airway remodeling in rats with chronic obstructive pulmonary disease.Methods SD rats were divided into control group,model group(chronic obstructive pulmonary disease model),experimental-L group(chronic obstructive pulmonary disease model,1.5 mg·kg-1 vitexin treatment),experimental-M group(chronic obstructive pulmonary disease model,3.0 mg·kg-1 vitexin treatment),experimental-H group(chronic obstructive pulmonary disease model,6.0 mg·kg-1 vitexin treatment),experimental-H+LPA group(chronic obstructive pulmonary disease mode,6.0 mg·kg-1 vitexin,lysophosphatidic acid 1 mg treatment),Western blot detection of RhoC protein expression,detection of pulmonary function indexes in rats,hematoxylin-eosin staining to observe lung histopathology,and evaluation of airway inflammation in rats score,airway smooth muscle thickness,enzyme-linked immunosorbent assay method to detect interleukin-6(IL-6)content in bronchoalveolar lavage fluid,immunohistochemistry to detect basic fibroblast growth factor(bFGF)in lung tissue.Results The expression levels of RhoC protein in the control group,model group,experimental-H group,and experimental-H+LPA group were 0.25±0.02,0.71±0.09,0.31±0.03,0.47±0.04;forced vital capacity(FVC)were(8.25±0.62),(4.12±0.24),(7.21±0.54),(6.44±0.52)mL;inflammation score were 0.52±0.04,2.54±0.15,1.23±0.11,1.79±0.32;smooth muscle thickness were(19.28±1.52),(28.43±1.74),(19.45±1.18),(25.85±1.57)μm;IL-6 content were(2.40±0.08),(5.67±0.44),(2.85±0.23),(4.01±0.29)ng·L-1;bFGF protein expression were 0.19±0.02,0.52±0.05,0.24±0.02,0.43±0.05.There were statistically significant differences in the above indicators between the model group and the control group,between the experimental-H group and the model group,and between the experimental-H+LPA group and the experimental-H group(all P<0.05).Conclusion Vitexin inhibits RhoC/Rock signaling to improve lung inflammation and airway remodeling in chronic obstructive pulmonary disease rats.
5.Research progress of biological targeted therapy for atopic dermatitis
Ying LIU ; Cai-Jun YAO ; Hui ZENG ; Ji-Fang CHEN ; Chun ZHOU
The Chinese Journal of Clinical Pharmacology 2024;40(5):768-772
Atopic dermatitis(AD)is the most common chronic inflammatory skin disease.For decades,the treatment of AD has been limited to local corticosteroid or calcineurin inhibitors,and light therapy or systemic immunosuppressive drug for moderate to severe AD patients.With the in-depth study of the pathogenesis of AD,many local and systemic targeted therapy drugs are being developed,which may change the treatment options of AD.This review combination with the latest clinical trials give a summarize on the type,mechanism,efficacy and safety of biological targeted therapy for AD,to provide a theoretical basis for the individualized treatment of AD.
6.Bioequivalence study of compound lidocaine cream in healthy Chinese subjects
Meng-Qi CHANG ; Yu-Qi SUN ; Qiu-Jin XU ; Xi-Xi QIAN ; Ying-Chun ZHAO ; Yan CAO ; Liu WANG ; Cheng ZHANG ; Dong-Liang YU
The Chinese Journal of Clinical Pharmacology 2024;40(9):1321-1326
Objective To study the pharmacokinetic characteristics of the test formulation of compound lidocaine cream and reference formulation of lidocaine and prilocaine cream in Chinese healthy subjects and to evaluate whether there is bioequivalence between the two formulations.Methods A single-center,single-dose,randomized,open-label,two-period,two-sequence,crossover design was used.This study included 40 healthy subjects,and in each period,test formulation or reference formulation 60 g was applied to the skin in front of both thighs(200 cm2 each side,a total of 400 cm2)under fasting conditions,and the drug was left on for at least 5 h after application.The concentrations of lidocaine and prilocaine in plasma were determined using liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.Pharmacokinetic parameters were calculated using WinNonlin 8.0 software to evaluate the bioequivalence of the two formulations.Results After the application of the test formulation compound lidocaine cream and the reference formulation lidocaine and prilocaine cream on both thighs of the subjects,the pharmacokinetic parameters of lidocaine in plasma were as follows:Cmax were(167.27±91.33)and(156.13±66.86)ng·mL-1,AUC0-t were(1 651.78±685.09)and(1 636.69±617.23)ng·mL-1·h,AUC0-∞ were(1 669.85±684.65)and(1 654.37±618.30)ng·mL-1·h,the adjusted geometric mean ratios were 104.49%,101.88%and 101.89%,respectively,with 90%confidence intervals of 98.18%-111.20%,97.80%-106.13%and 97.87%-106.07%,all within the range of 80.00%-125.00%.The pharmacokinetic parameters of prilocaine in plasma were as follows:Cmax were(95.66±48.84)and(87.52±39.16)ng·mL-1,AUC0-t were(790.86±263.99)and(774.14±256.42)ng·mL-1·h,AUC0_m were(807.27±264.67)and(792.84±254.06)ng·mL-1 h,the adjusted geometric mean ratios were 107.34%,103.55%and 102.98%,respectively with 90%confidence intervals of 101.69%-113.31%,99.94%-107.30%and 99.65%-106.43%,all within the range of 80.00%-125.00%.Conclusion The test formulation compound lidocaine cream and the reference formulation lidocaine and prilocaine cream are bioequivalent.
7.Safety and efficacy of colon polypectomy in patients taking antithrombotic drugs
Chen MU ; Han ZHANG ; Ying LIU ; Xue LI ; Rui GU ; Chun-Yan CAO ; Xu GUO
Modern Interventional Diagnosis and Treatment in Gastroenterology 2024;29(6):660-663
Objective To investigate the safety and effectiveness of colon polypectomy in patients taking antithrombotic drugs.Methods Polyps treated with endoscopic polypectomy at the Department of Gastroenterology,Fu Wai Hospital,Chinese Academy of Medical Sciences,from August 2022 to August 2023 were retrospectively analyzed for the site of polyp,postoperative delayed hemorrhage,perforation,and the completeness of resection,specimen retrieval,and the occurrence of postoperative ischemic events.Results A total of 103 polyps were included in the study,which were divided into two groups according to whether the diameter of the polyp was>10 mm(87 cases in the small polyp group vs 16 cases in the large polyp group),and there was no statistically significant difference between the two groups in terms of the site of the polyp,its morphology,the type of antithrombotic drug taken,the rate of curative resection,the rate of postoperative hemorrhagic events,and the incidence of postoperative ischemic events;the large polyp group chose more often to undergo EMR treatment(small polyp group vs.large polyp group,4.6%vs.45.5%,P=0.004);postoperative pathology was more adenomatous polyps in the large polyp group(small polyp group vs.large polyp group,77.0%vs.93.8%,P=0.027).Conclusion Endoscopic polypectomy can be used safely and effectively in patients taking antithrombotic drugs.
8.Short-term substitution of calcineurin inhibitors (CNI) with recombinant humanized anti-CD25 monoclonal antibody (Basiliximab) as aGVHD prophylaxis in CNI intolerant patients after allogeneic hematopoietic stem cell transplantation
Shan SHAO ; Huixia LIU ; Ying JIANG ; Su LI ; Daolin WEI ; Jun ZHU ; Chun WANG ; Chuxian ZHAO
Chinese Journal of Hematology 2024;45(2):115-120
Objectives:To investigate the efficacy of short-term substitution of recombinant humanized anti-CD25 monoclonal antibody (Basiliximab) as acute GVHD (aGVHD) prophylaxis in calcineurin inhibitors (CNI) intolerant patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:This study included 17 patients with refractory malignant hematological disorders who underwent salvage allo-HSCT at the Bone Marrow Transplantation Department of Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from August 2021 to August 2022 and were treated with Baliximab to prevent aGVHD due to severe adverse reactions to CNI. There were seven men and ten women, with a median age of 43 years (18-67). Following the discontinuation of CNI, Basiliximab was administered at a dose of 1 mg/kg once weekly until CNI or mTOR inhibitors were resumed.Results:Basiliximab was started at an average of 5 (1-32) days after HSCT. The median duration of substitution was 20 (7-120) days. All had neutrophil engraftment within a median of 12 (10-17) days. Thirteen patients had platelet engraftment after a median of 13 (11-20) days. Four patients did not develop stable platelet engraftment. Eight patients (47.1% ) developed Grade Ⅱ-Ⅳ aGVHD, while four (23.6% ) developed Grade Ⅲ/Ⅳ aGVHD. Only one patient died from aGVHD. Before the end of the followup period, seven of 17 patients died. The longest followup period of the survivors was 347 days, and the median survival rate was not met. The overall survival (OS) rate at six months was 62.6%. Among the 17 patients, 13 (76.4% ) experienced cytomegalovirus reactivation, 7 (41.2% ) experienced EB virus activation, and no cytomegalovirus disease was observed.Conclusions:When CNI intolerance occurs during allo-HSCT, short-term replacement with Baliximab can be used as an alternative to prevent aGVHD.
9.Selected donor CD34 + cell boosts for salvage treatment of poor graft function following allogeneic hematopoietic stem cell transplantation in primary myelofibrosis: 3 cases report
Haixia SHI ; Huixia LIU ; Daolin WEI ; Jun ZHU ; Shan SHAO ; Ying JIANG ; Chun WANG ; Chuxian ZHAO
Chinese Journal of Hematology 2024;45(8):785-788
A retrospective analysis was conducted on three patients with primary myelofibrosis who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from 2020 to 2023. They subsequently developed poor graft function. The patients received selected donor CD34 + cell boosts as salvage therapy. There were two male patients and one female patient, with a median age of 68 (39-69) years. The median time from allo-HSCT to the selected donor CD34 + cell boost was 83 (56-154) days. The median infusion of selected donor CD34 + cells was 7.67 (7.61-9.06) ×10 6/kg, with a CD34 + cell purity of 97.76% (96.50%-97.91%) and a recovery rate of 70% (42%-75%) . Hematological recovery was achieved in two cases. No acute GVHD was observed in any of the three patients. One case of moderate oral chronic GVHD was noted. Selected donor CD34 + cell boosts for the treatment of poor graft function after allo-HSCT in primary myelofibrosis was effective and no severe acute or chronic GVHD was observed.
10.Distribution Patterns of Traditional Chinese Medicine Constitution in 959 Patients with Endometriosis
Xin-Chun YANG ; Wei-Wei SUN ; Ying WU ; Qing-Wei MENG ; Cai XU ; Zeng-Ping HAO ; Yu-Huan LIU ; Rui-Jie HOU ; Rui-Hua ZHAO
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1387-1392
Objective To investigate the distribution patterns of traditional Chinese medicine(TCM)constitution in 959 patients with endometriosis(EMs).Methods From January 2019 to November 2019,959 EMs patients were selected from Guang'anmen Hospital of China Academy of Chinese Medical Sciences,Beijing Obstetrics and Gynecology Hospital Affiliated to Capital Medical University,Beijing Hospital,Dongfang Hospital of Beijing University of Chinese Medicine,Beijing Friendship Hospital Affiliated to Capital Medical University,and Fuxing Hospital Affiliated to Capital Medical University.The general clinical information of the patients was recorded and then the TCM constitution was identified.After that,the correlation of TCM constitution distribution with concurrent constitution and the relationship of TCM constitution distribution with age and the complication of dysmenorrhea were analyzed.Results(1)The constitution types of EMs patients listed in descending order of the proportion were yang deficiency constitution(65.1%,624/959),qi stagnation constitution(58.4%,560/959),qi deficiency constitution(52.8%,506/959),blood stasis constitution(44.2%,424/959),phlegm-damp constitution(42.5%,408/959),damp-heat constitution(41.9%,402/959),yin deficiency constitution(39.6%,380/959),balanced constitution(26.8%,257/959),and inherited special constitution(16.6%,159/959).Among the patients,there were fewer patients with single constitution,accounting for 20.2%(194/959),and most of them had concurrent constitution types,accounting for 79.8%(765/959).(2)The association rule mining based on Apriori algorithm obtained 33 related rules.The concurrent constitution types of qi deficiency-yang deficiency,blood stasis-yang deficiency,and blood stasis-qi stagnation were the association rules with high confidence.(3)Compared with patients aged 35 years and below,the patients over 35 years old were predominated by high proportion of blood stasis constitution(P<0.05).Compared with patients without dysmenorrhea,the patients with dysmenorrhea had the increased proportion of biased constitutions and the decreased proportion of balanced constitution(P<0.05 or P<0.01).Conclusion Yang deficiency constitution,qi stagnation constitution,qi deficiency constitution and blood stasis constitution are the high-risk constitution types of EMs patients.The concurrent constitution types are commonly seen in EMs patients,which are more common than single biased constitution.Management of EMs patients with the methods of warming yang,relieving stagnation,benefiting qi and activating blood will be helpful for correcting the biased constitutions in time and preventing disease progression,which will achieve the preventive treatment efficacy through TCM constitution correction.

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