1.Analysis of xenobiotics in colon and immune tissues of ulcerative colitis mice after administration of Sini San by LC-MS
Yanfang CAO ; Yali WANG ; Anhui WANG ; Yongshun CHEN ; Sihan LI ; Kai FENG ; FENG YANG ; Rui SONG
Journal of China Pharmaceutical University 2025;56(1):73-79
Dysregulation of immune response is currently recognized as one of the important pathological factors in ulcerative colitis (UC). Based on the confirmation that the Sini San (SNS) can significantly improve the colon inflammation induced by dextran sulfate sodium sulfate (DSS) in mice, the present work systematically studied the xenobiotics in the colon and mesenteric lymph nodes, spleen, and thymus of UC mice after administration of SNS by high-performance liquid chromatography-ion trap time-of-flight mass spectrometry (HPLC-IT-TOF-MS). The results showed that, in addition to the colon, some components and their metabolites in SNS could be distributed in immune tissues, and it was found that the quality of relatively low-abundance and weakly responsive components such as saikosaponin a, paeoniflorin, and glycyrrhizic acid had the characteristics of efficient transmission to the colon and lymphoid organs. These components were very likely to be the source of pharmacodynamic substances of SNS. The findings of this study lay a foundation for the study of the efficacy and molecular mechanism of the components against ulcerative colitis, and also provide a scientific basis for the rational clinical application of SNS, which is expected to promote the secondary development of its preparations.
2.Inhibition of PCV2 on IL-15 in inguinal lymph nodes of piglets
Yanan ZHANG ; Feiyan WANG ; Chen YUAN ; Jing REN ; Kai SU ; Huaining YUE ; Shuanghai ZHOU ; Huanrong LI ; Qinye SONG
Chinese Journal of Veterinary Science 2024;44(8):1593-1599,1621
Porcine circovirus type 2(PCV2)mainly damages the immune cells of pigs,causing lym-phocyte depletion and immune suppression.Interleukin(IL)-15 regulates immune functions wide-ly,and plays an important regulatory role in the survival,proliferation,differentiation and immune function of a variety of immune cells such as natural killer(NK),CD8+T cells and NKT cells.In this study,in order to determine the effect of PCV2 on IL-15 expression,4-week-old piglets(n=4)were infected with PCV2 and the negative control group(n=4)was set up.On day 7 post-infec-tion,the inguinal lymph nodes of the infected and control groups were collected,and porcine cyto-kine antibody microarray(QAP-CYT-1)was employed to quantify the expression of cytokines in the tissues,screen for differential cytokines,and GO and KEGG enrichment analysis for IL-15 were conducted.Real-time quantitative fluorescent PCR(qPCR)and ELISA were used to verify the level of IL-15 mRNA and protein,and those in porcine peripheral blood mononuclear cells(PBMC)and serum were simultaneously detected.Compared with the negative control group,the expression lev-el of IL-15 was significantly reduced in the infected group(P<0.05);IL-15 was mainly involved in cytokine-cytokine receptor interactions,immune responses,cellular activation,and the regulation of JAK-STAT and TNF signaling pathways.The levels of IL-15 mRNA and protein in inguinal lymph nodes in the infected group were significantly lower than those in the control group(P<0.05),which was consistent with the detection results of QAP-CYT-1.However,there was no significant difference in IL-15 mRNA and protein levels in PBMC and serum.These results indicate that PCV2 can inhibit IL-15 in the inguinal lymph node microenvironment of piglets.This study can provide important information for further revealing the immunosuppressive mechanism of PCV2.
3.Relationship between prognostic nutritional index and risk of functional dependence in maintenance hemodialysis patients
Ci SUN ; Kai SONG ; Shan JIANG ; Ying LU ; Peiran YIN ; Weiwei LI
Chinese Journal of Nephrology 2024;40(9):691-697
Objective:To evaluate the relationship between prognostic nutritional index (PNI) and risk of functional dependence in patients receiving maintenance hemodialysis (MHD).Methods:It was a cross-sectional survey study. The clinical data of MHD patients in the Second Affiliated Hospital of Soochow University from June to December 2023 were collected. The Katz and Lawton-Brody questionnaires were used to assess the functional status. The patients were divided into normal functional status group and functional dependence group, and the differences of the clinical data between the two groups were compared. Serum albumin and lymphocytes were used to determine PNI, and the patients were divided into four subgroups: Q1 group (PNI≤44.3), Q2 group (44.3
4.The value of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer at different risk of brain metastasis
Xingyue LI ; Meng YAN ; Song GUAN ; Jia TIAN ; Jianian LAI ; Chunliu MENG ; Jintao MA ; Kai REN ; Xue LI ; Lujun ZHAO
Chinese Journal of Radiation Oncology 2024;33(7):606-613
Objective:To establish a brain metastasis (BM) prediction model for limited-stage small cell lung cancer (LS-SCLC) patients who achieved complete response (CR) or partial response (PR) after thoracic chemoradiotherapy, and to explore the value of prophylactic cranial irradiation (PCI) in different risk groups.Methods:Clinical data of 274 patients with LS-SCLC who achieved CR/PR after thoracic chemoradiotherapy in Tianjin Medical University Cancer Institute & Hospital from January 2010 to December 2021 were retrospectively analyzed, including 144 cases in the PCI group and 130 in the non-PCI group. The nomogram was developed based on variables determined by univariate and multivariate analyses in the non-PCI group. The bootstrap method, receiver operating characteristics (ROC) curve, calibration curve and decision curve analysis (DCA) were employed to evaluate the predictive power and clinical benefits of the model. Patients were stratified into high- and low-risk groups based on risk scores. The brain metastases-free survival (BMFS), progression-free survival (PFS), extracranial progression-free survival (ePFS) and overall survival (OS) were compared between patients with and without PCI in different risk-stratified populations using the log-rank test.Results:The nomogram included five variables: systemic immune inflammation index (SII), lymphocyte-to-monocyte ratio (LMR), pro-gastrin-releasing peptide precursor (ProGRP), neuron-specific enolase (NSE), and blood calcium. The area under the ROC curve (AUC) of the nomogram in predicting 1- and 2-year BMFS was 0.761 and 0.822. In the low-risk group, there was no significant difference in the BMFS ( P=0.374), PFS ( P=0.551), ePFS ( P=0.508) and OS ( P=0.767) between the PCI and non-PCI groups. In the high-risk group, PCI could significantly increase the BMFS ( P<0.001) and PFS ( P=0.022), while there was no significant difference in the ePFS ( P=0.963) and OS ( P=0.632). And propensity score-matching (PSM) analysis showed similar results. Conclusions:PCI does not improve OS in LS-SCLC patients regardless of high or low risk of BM. However, PCI significantly prolong the BMFS and PFS in patients at a high risk of BM.
5.Current Situation,Existing Problems and Solving Strategies of the Assessment of Medical Ethics and Styles in the Examination of Doctors' Qualification
Hua GUO ; Yu HAN ; Kai REN ; Zhihao ZHOU ; Mingjie ZI ; Yujiao SONG ; Min ZHU ; Lili XYU ; Yi LI ; Tingting WANG ; Linyong YU
Journal of Traditional Chinese Medicine 2024;65(12):1292-1295
This paper discussed the current education status on medical ethics and styles and the assessment condition in the examination of doctors' qualification, as well as the existing problems and potential solutions by reviewing domestic and foreign literature and summarizing the practice experience. Traditionally, medical ethics and styles have always been integrated into clinical medical practice in China. However, under the modern medical education system, it is challenged to integrate traditional education on medical ethics and styles with the rules of modern medical knowledge. By summarizing the education and assessment status of medical ethics and styles in the examination of doctors' qualification, it is found that the current examination is relatively poor in the evaluation content, and the way of evaluation is not diverse, with lack of curriculum of medical humanities. The solutions suggested are enriching relevant examination content, introducing more and comprehensive evaluation method, and establishing more medical humanities-related courses.
6.Efficacy of XELOX regimen neoadjuvant chemotherapy in the treatment of stage Ⅱ(T4)and Ⅲ colon cancer
Shaoyi WANG ; Kai NIE ; Ranran LI ; Dafeng CHEN ; Xiaojun XUE ; Lei YE ; Jianping LIU ; Song ZHOU
Journal of Clinical Surgery 2024;32(2):188-191
Objective To evaluate the efficacy of XELOX regimen as neoadjuvant chemotherapy in the treatment of stage Ⅱ and Ⅲ colon cancer.Methods The clinical data of 50 patients with clinical stage Ⅱ(T4)Ⅲ colon cancer who underwent laparoscopic radical resection at general surgery department of our hospital from January 1,2012 to January 1,2021 were retrospectively analyzed.Patients were divided into neoadjuvant chemotherapy group(NACT)and adjuvant chemotherapy group(ACT)according to whether they received neoadjuvant chemotherapy with XELOX regimen.The general clinical data,adverse reactions of chemotherapy,surgical complications,operation time,intraoperative blood loss,hospitalization time,hospitalization cost,negative conversion rate of tumor markers,tumor remission rate,tumor downstaging rate,tumor response grade after chemotherapy,postoperative disease-free survival curve,and overall survival curve were retrospectively analyzed and compared among the groups.Results There were no significant differences in operative complications,postoperative exhaust time and hospital stay between NACT group and ACT group(P>0.05).The adverse reactions of chemotherapy,the negative conversion rate of postoperative CEA and CA19-9,the duration of operation,the amount of bleeding,and the hospitalization cost in NACT group were significantly better than those in ACT group(P<0.05).In terms of DFS and OS survival curves,with the extension of time,the decline of the NACT survival curve was smaller than that of the ACT group,and there was a significant difference in DFS survival curve(P<0.05),but no significant difference in OS survival curve(P>0.05).Conclusion XELOX neoadjuvant chemotherapy is safe and effective in the treatment of stage Ⅱ(T4)and stage Ⅲcolon cancer.
7.Design of assisted patient conveying and vibration damping system
Jian YOU ; Jing-Yi WANG ; Wei-Qiang GAO ; Min-Tang LI ; Kai SONG ; Lin-Lin ZHANG ; Chang-Yi CHEN
Chinese Medical Equipment Journal 2024;45(1):15-24
Objective To design an assisted patient conveying and vibration damping system to solve the problems of operator fatigue and patient bump during casualty evacuation.Methods The assisted patient conveying and vibration damping system was composed of several conveying straps and a vibration damping mechanism.The conveying straps were made up of a waist strap,two shoulder straps,a chest strap,adhesive straps and joint components,and the joint components included adjusting buckles,big buckles,small buckles,connecting buckles and hook mechanisms;the vibration damping mechanism adopted the technical form of extension handle combined with vibration absorber,in which the extension handle was made of rigid material and the vibration absorber was equipped with a scissor guiding mechanism.Tests were carried out on the system to record the operating time of the operators and to analyze the system's vibration damping characteristics.Results The system developed extended the operating time of the stretcher conveyers while reduced the vibration during casualty transport,with a maximum vibration reduction of 71.73%.Conclusion The system developed gains advantages in low vibration and low workload,and can be used for casualty conveying in poor road conditions.[Chinese Medical Equipment Journal,2024,45(1):15-24]
8.Clinical trial of parecoxib sodium combined with dexmedetomidine for surgery in patients with osteoporotic compression fractures
Kai LUO ; Qing WANG ; Gao-Ju WANG ; Jin YANG ; Guang-Zhou LI ; Shi-Jie SONG ; Shun-Gui CAI
The Chinese Journal of Clinical Pharmacology 2024;40(20):2963-2967
Objective To investigate the effects of parecoxib sodium injection combined with dexmedetomidine hydrochloride injection on postoperative cognitive function and stress response in patients with osteoporotic compression fractures.Methods The patients with osteoporotic compression fractures were divided into treatment group and control group according to the treatment plan.The control group was given intravenous injection of dexmedetomidine hydrochloride injection 0.2 μg·kg-1load dose,then micro pump injection 0.2 μg·kg-1·min-1 maintenance dose,until 30 min before the end of the operation;patients in the treatment group were intravenously injected with parecoxib sodium injection 20 mg before local anesthesia and 30 min before the end of operation on the basis of the control group.The pain,sedation,hemodynamics[mean arterial pressure(MAP),heart rate(HR)],cognitive function and safety evaluation were compared between the two groups before operation(T0),2 h after operation(T1),6 h after operation(T2),12 h after operation(T3)and 24 h after operation(T4).Results There were 39 cases in the treatment group and 41 cases in the control group.Visual analogue scale(VAS)scores in treatment group and control group were(3.09±0.55)and(3.41±0.62)scores at T1;VAS scores were(3.02±0.57)and(3.35±0.48)scores at T2;VAS scores were(2.64±0.44)and(2.90±0.46)scores at T3;VAS scores were(2.02±0.41)and(2.35±0.47)scores at T4;MMSE scores were(25.28±1.57)and(24.33±1.42)scores at T2;MMSE scores were(28.16±1.01)and(27.25±0.89)scores at T4;MoCA scores were(24.63±1.60)and(23.59±1.25)scores at T2;MoCA scores were(27.20±0.97)and(26.48±0.83)scores at T4.There were statistically significant differences in the above indexes between the treatment group and the control group(all P<0.05).Adverse drug reactions in the treatment group included bradycardia,hypotension,nausea vomiting and hypokalemia;adverse drug reactions in the control group included bradycardia,hypotension and nausea vomiting.The total incidence rates of adverse drug reactions were 12.82%and 9.76%,without statistically significant difference(P>0.05).Conclusion Compared with using dexmedetomidine alone,parecoxib sodium combined with dexmedetomidine is beneficial for relieving postoperative pain in patients with osteoporotic compression fractures,improving postoperative cognitive function.
9.Effect of Tongfeng Decoction (痛风汤) on NLRP3 Inflammatory Vesicles and Neutrophil Extracellular Traps in Synovial Tissues of Ankle Joints in Acute Gouty Arthritis Model Rats
Yongzheng DENG ; Qingliang MENG ; Junfu MA ; Jiakang CUI ; Kai LI ; Gengfeng WANG ; Chenyang SONG ; Hua BIAN
Journal of Traditional Chinese Medicine 2024;65(17):1816-1824
ObjectiveTo explore the possible mechanism of Tongfeng Decoction (痛风汤) for preventing and treating acute gouty arthritis. MethodsSixty Wistar male rats were divided into normal group, model group, colchicine group and low-, medium- and high-dose Tongfeng Decoction groups according to the random number table, 10 rats in each group. Tongfeng Decoction of 11.34, 22.68 and 45.36 g/kg were given by gavage to low-, medium- and high-dose Tongfeng Decoction groups, colchicine 3.15×10-4 g/(kg·d) to the colchicine group, and normal saline 10 ml/(kg·d) to the normal group and model group respectively for 7 consecutive days. After 1 hour of gavage on day 5, rats in all groups except the normal group were modelled as acute gouty arthritis in the ankle joint of the right hind limb with the modified Coderre's method; rats in the normal group were injected with 0.2 ml of normal saline at the same location. The swelling degree of the ankle joint was measured before modelling and after 6 h, 12 h, 24 h and 48 h of modelling, respectively. HE staining was used to observe the histopathological and morphological changes in the synovial tissue of the ankle joint; immunoblotting and RT-qPCR were used to detect NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteine aspartate protease 1 (Caspase-1), and interleukin 1β (IL-1β) protein and mRNA expression levels in ankle synovial tissues, respectively; immunohistochemistry was used to detect the positive expression of Caspase-1 and IL-1β in ankle synovial tissues; ELISA was used to detect the tumour necrosis factor alpha (TNF-α), IL-1β, and interleukin in serum; immunofluorescence staining was used to observe the formation of neutrophil extracellular traps (NETs) in the synovial tissues of the ankle joints. ResultsCompared with the normal group, rats in the model group showed elevated joint swelling at all time points, significantly increased inflammatory cell infiltration and the number of synovial cell layers in the synovial tissues of the ankle joints, elevated NLRP3, Caspase-1, ASC and IL-1β protein and mRNA expression, elevated positive expression of Caspase-1 and IL-1β, increased formation of NETs, and elevation of TNF-α, IL-6, and IL-1β in serum (P<0.05). Compared with the model group, there was an improvement in synovial cell proliferation and inflammatory cell infiltration of the ankle joint in the colchicine group, high- and medium-dose Tongfeng Decoction groups. In the colchicine group and the high-, medium- and low-dose Tongfeng Decoction groups, the degree of joint swelling, positive expression of Caspase-1, IL-1β and formation of NETs in the synovial tissue of the ankle joint, and TNF-α, IL-6 and IL-1β in serum reduced 24 h and 48 h after modelling; in colchicine group and high-dose Tongfeng Decoction group, NLRP3, ASC, Caspase-1, IL-1β protein and mRNA expression in the synovial tissues of ankle joints all reduced (P<0.05). The colchicine group and high-dose Tongfeng Decoction group were superior to the low-dose Tongfeng Decoction group in reducing ASC, Caspase-1, IL-1β protein and mRNA expression in the ankle synovial tissues, the positive expression of Caspase-1, as well as TNF-α, IL-6, and IL-1β level in serum (P<0.05). ConclusionTongfeng Decoction showed effectiveness for the prevention and treatment of acute gouty arthritis, and its mechanism may be related to the inhibition of the assembly and activation of NLRP3 inflammatory vesicles in ankle synovial tissues, the inhibition of the release of inflammatory factors, and the formation of NETs.
10.Construction, Activity Evaluation and Molecular Simulation Study of α-Naphthylthiol Amino Acid Esters as Novel LSD1 Inhibitors
Zhonghua LI ; Zhenzhen WANG ; Tingting QIN ; Pan WANG ; Kai HU ; Zhishen XIE ; Lixin LI ; Xiaowei ZHANG ; Junying SONG ; Weihong REN ; Jinlian MA
Chinese Journal of Modern Applied Pharmacy 2024;41(3):295-302
OBJECTIVE
To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation.
METHODS
Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation.
RESULTS
A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions.
CONCLUSION
The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.


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