1.Efficacy of rituximab therapy for 10 patients suffering from systemic lupus erythematosus with intestinal involvement
Yurong ZHAO ; Zheng ZHAO ; Jie ZHANG ; Kunpeng LI ; Jinshui YANG ; Fei SUN ; Simin LIAO ; Jianglin ZHANG ; Feng HUANG ; Jian ZHU
Chinese Journal of Internal Medicine 2024;63(2):198-202
We retrospectively analyzed therapy efficacy and the adverse reactions of 10 patients suffering from systemic lupus erythematosus (SLE) with intestinal involvement treated with rituximab (RTX). Patients were hospitalized in the Department of Rheumatology and Immunology of the First Medical Center of PLA General Hospital from January 2015 to January 2023. Among the 10 patients, two were men and eight were women. The age of the cohort was (41.9±8.8) years. The age at disease onset was (28.8±9.2) years. The total course of the SLE diagnosis was(109.6±59.9) months. The course of the diagnosis of SLE with intestinal involvement was (89.3±50.2) months. The time from the appearance of intestinal symptoms to the diagnosis of SLE with intestinal involvement was 1.5 (1.0,8.0) months. The time from the diagnosis of SLE with intestinal involvement to RTX use was 13.0 (1.0,46.3) months. Follow-up duration after application of RTX treatment was (55.3±28.4) months. There were five cases of abdominal pain, four cases of abdominal distension, nine cases of diarrhea, three cases of nervous-system involvement, nine cases of lupus nephritis, and seven cases of serositis. All 10 patients underwent computed tomography and radiology of the abdomen. Eight patients had intestinal-wall edema, seven suffered intestinal dilation, four had target signs, three suffered congestion of mesenteric blood vessels, eight had increased mesenteric-fat density, and six had false intestinal obstruction. All 10 patients showed a low level of complement C3 (250-750 mg/L). Nine cases showed a low level of complement C4 (10-90 mg/L). The SLE disease activity index 2000 (SLEDAI-2K) at baseline in 10 patients was 20.5 (17.8, 30.0). After receiving RTX (0.5 g: day 1, day 14, or 375 mg/m 2: day 1, day 14) induction treatment, the intestinal symptoms of 10 cases were relieved completely. Four patients had adverse reactions, of which three received a high-dose glucocorticoid combined with RTX treatment simultaneously. Adverse reactions manifested mainly as a reduced level of IgG and infection with herpes simplex virus in one case, reduced level of IgG and lung infection in one patient, lung infection in one case, and reduced IgG level in one patient. RTX may an efficacious treatment strategy for patients suffering from refractory SLE with intestinal involvement.
2.Study on the mechanism of action of Siheifang on zebrafish melanin based on metabolomics and network pharmacology
Qihui SU ; Jing WANG ; Rongrong LUO ; Yurong HUANG ; Xin LI ; Yingli WANG ; Ying JIA
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(9):988-1001
AIM:To study the mechanism of Sihei-fang(SHF)in improving pigment deficiency disease(PD)by combining network pharmacology and me-tabolomics.METHODS:Using zebrafish embryos with pigment deficiency disease induced by 1-phe-nyl-2-thiourea(PTU)as an animal model,the ef-fects of SHF extract(0.01,0.02,0.04 mg/mL)on the morphology,melanin area,tyrosinase activity,and melanin content of zebrafish embryos were an-alyzed.Ultra high performance liquid chromatogra-phy-mass spectrometry(UHPLC-MS)was used to screen differential metabolites and obtain relevant metabolic pathways in the SHF treatment of mela-nin deficient zebrafish embryos model.Network pharmacology was used to obtain key targets for SHF treatment of PD and conduct KEGG pathway enrichment analysis.Import The identified differen-tial metabolites and SHF PD intersection targets were imported into the Metscape plugin,to estab-lish a"metabolite reaction enzyme gene"network,and search for key metabolites,targets,and meta-bolic pathways.RESULTS:SHF treatment could in-crease the formation of zebrafish melanin,activate tyrosinase activity,and increase melanin content.Metabolomics analysis obtained 54 differential me-tabolites,and metabolic pathway analysis was con-ducted on these metabolites,involving the biosyn-thesis of phenylalanine,tyrosine,and tryptophan,glycerol phospholipid metabolism,tyrosine metab-olism,linoleic acid metabolism,and aminoacyl tRNA biosynthesis pathways.Network pharmacolo-gy had obtained 55 cross targets of components and diseases.KEGG involved pancreatic cancer,TNF,cancer and other signal pathways.The joint analysis of metabolomics and network pharmacolo-gy identified four key targets:COMT,CYP1B1,TYR,and ALDH2;three key metabolites:L-tyrosine,ho-movanllate,L-lysine;three important metabolic pathways:tyrosine metabolism,valine/leucine/iso-leucine degradation,and lysine metabolism.CON-CLUSION:SHF has a good improvement effect on PD,and combined with metabolomics and network pharmacology,SHF may enhance its influence on the tyrosine metabolism pathway by regulating the metabolite L-tyrosine,thereby promoting the for-mation of melanin.
3.Xinfeng capsule inhibits rheumatoid arthritis by binding to Wnt5a via Wnt/β-catenin signaling pathway
Yurong HUANG ; Yanhui PENG ; Bing WANG ; Chenggui MIAO ; Xiao WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(10):1134-1145
AIM:This study will clarify whether Wnt5a can be used as a potential diagnostic and therapeutic target for rheumatoid arthritis(RA)and how Xinfeng capsule(XFC)can improve RA through the Wnt5a/β-catenin signaling pathway.METH-ODS:ELISA and RT-qPCR were used to detect in-flammatory factors and pathological genes in the rat model of AA in vivo to investigate the effect of XFC on AA rats.RT-qPCR was used to verify the core genes and key pathways of XFC regulation pre-dicted by network pharmacology.The regulatory mechanism of XFC on Wnt/β-catenin pathway was elucidated by RT-qPCR.Western blot and immuno-fluorescence in primary AA fibroblast-like synovial cells(FLS)in vitro.RESULTS:XFC significantly de-creased the arthritis score and paw swelling in AA rats,and inhibited joint inflammation in AA rats.XFC decreased the levels of inflammatory factors TNF-α and IL-1 in peripheral blood of AA rats,and inhibited the levels of pathological genes MMP3 and fibronectin in joint synovium and AA FLS of AA rats.Network pharmacology predicts that the Wnt pathway is highly correlated with XFC treatment of RA.At the cellular level,serum containing XFC in-hibited the expression of Wnt pathway-related genes β-catenin,CCND1 and c-Myc.The molecular docking results showed that the key components of XFC had strong binding ability to Wnt5a,and the overexpression of Wnt5a(Wnt5a-ove)in AA FLS in-terfered with the action of XFC.CONCLUSION:The expression of Wnt5a is significantly increased in AA FLS and RA FLS,and XFC can inhibit the activation of Wnt/β-catenin signaling pathway to improve RA by binding with Wn5a,providing a new therapeutic mechanism for XFC to improve RA.
4.A case of successful treatment of an extremely preterm infant born at 21 weeks and 4 days of gestation
Haifeng ZONG ; Bingchun LIN ; Yingsui HUANG ; Shan JIANG ; Yurong YUAN ; Xiaoyun XIONG ; Zhifeng HUANG ; Chuanzhong YANG
Chinese Journal of Perinatal Medicine 2024;27(10):860-864
This case report described the sucussful treatment of a male infant born at 21 weeks and 4 days through assisted reproductive technology. After prenatal consultation and with the strong desire of the parents, active resuscitation and treatment were performed. The infant received 52 days of mechanical ventilation and was extubated to non-invasive ventilation at a corrected gestational age of 28 weeks and 6 days. During hospitalization, no vasoactive drugs were used, and necrotizing enterocolitis did not occur. The gastric tube was removed at a corrected gestational age of 37 weeks and 4 days. At a corrected gestational age of 40 weeks, cranial MRI showed no abnormalities. The infant was discharged at a corrected gestational age of 42 weeks after 143 days of treatment, without the need for any respiratory support. Follow-up until a corrected age of 6 months showed good growth and development.
5. Study on the improvement of Qingdaipowder Gel for external use on mice with specific dermatitis
Yurong HUANG ; Yan WANG ; Jie FAN ; Yingli WANG ; Ying JIA ; Hongqiang ZHANG ; Rongli YOU
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(1):19-28
AIM: To study the effect of Qingdaipowder Gel (QDPG) on mice specific dermatitis (AD) model and the antibacterial effect of the ethanol extract of Qingdaipowder. METHODS: AD model of mice was established by repeated skin induction with 2,4-dinitrochlorobenzene (DNCB). Fifty-six mice were randomly divided into blank group, model group, Hydrocortisone Butyrate Cream group (Hyd, 1.5 mg/cm
6. Mechanism of compound kushen injection in the treatment of lung cancer based on serum metabolomics and network pharmacology
Rongli YOU ; Rongli YOU ; Lina HAI ; Yurong HUANG ; Yan WANG ; Rui MAO ; Yingli WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(9):988-999
AIM: To explore the mechanism of action of alkaloid components of compound kushen Injection (CKI) in the treatment of lung cancer based on serum metabolomics, network pharmacology, and molecular docking techniques. METHODS: A lung cancer model was established in C57 mice by inoculation of Lewis mouse lung cancer tumor strain. Thirty male mice were randomly divided into normal group, model group and CKI group. The drug was administered by tail vein injection once daily for 17 consecutive days. Mouse serum was examined by ultrahigh performance liquid chromatography tandem mass spectrometry (LC-MS) metabolomics, and several multivariate statistical analyses including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), combined with databases such as the human metabolic database (HMDB) and related literature to identify and identify differential metabolites, the relevant metabolic pathways were searched for by the metaboanalyst online tool. Using network pharmacology, construct the“component-target-disease”network of CKI in the treatment of lung cancer. Molecular docking method was used to verify the interaction between potential active ingredients and core targets. Serum metabolomics was jointly analyzed with network pharmacology to construct a“metabolite-germinal-enzyme-gene” network. RESULTS: Through metabolomics technology, 16 differential metabolites associated with lung cancer were screened from serum, and CKI addback these differential metabolite levels compared with the model group. Metabolic pathways mainly involve retinol metabolism, tryptophan metabolism, glycerophospholipid metabolism and other metabolic pathways. Network pharmacology analysis indicated that CKI treatment of lung cancer mainly targets STAT3, MAPK3, and MAPK1, which are closely related to proteoglycans, cellular senescence, and HIF − 1 signaling pathways in cancer. CONCLUSION: This article explains the mechanism of CKI in treating lung cancer from the perspective of metabonomics and network pharmacology, and provides basis for further study of CKI.
7.Characterization of natural peptides in Pheretima by integrating proteogenomics and label-free peptidomics
Xiaoxiao LUO ; Qirui BI ; Dongdong HUANG ; Yun LI ; Changliang YAO ; Jianqing ZHANG ; Wenlong WEI ; Jiayuan LI ; Zhenwei LI ; Jingxian ZHANG ; Shen JI ; Yurong WANG ; De-An GUO
Journal of Pharmaceutical Analysis 2023;13(9):1070-1079
Pheretima,also called"earthworms",is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines(CPMs)in Chinese Pharmacopoeia(2020 edi-tion).However,its zoological origin is unclear,both in the herbal market and CPMs.In this study,a strategy for integrating in-house annotated protein databases constructed from close evolutionary relationship-sourced RNA sequencing data from public archival resources and various sequencing al-gorithms(restricted search,open search,and de novo)was developed to characterize the phenotype of natural peptides of three major commercial species of Pheretima,including Pheretima aspergillum(PA),Pheretima vulgaris(PV),and Metaphire magna(MM).We identified 10,477 natural peptides in the PA,7,451 in PV,and 5,896 in MM samples.Five specific signature peptides were screened and then validated using synthetic peptides;these demonstrated robust specificity for the authentication of PA,PV,and MM.Finally,all marker peptides were successfully applied to identify the zoological origins of Brain Heart capsules and Xiaohuoluo pills,revealing the inconsistent Pheretima species used in these CPMs.In conclusion,our integrated strategy could be used for the in-depth characterization of natural peptides of other animal-derived traditional Chinese medicines,especially non-model species with poorly annotated protein databases.
8.Effects of dexmedetomidine on stress response and postoperative recovery in children undergoing laparoscopic surgery
Yurong HUANG ; Xinxing HUANG ; Weiwei KE
Chinese Journal of Primary Medicine and Pharmacy 2023;30(10):1523-1528
Objective:To investigate the effects of dexmedetomidine on stress response and postoperative recovery in children undergoing laparoscopic surgery.Methods:A total of 200 pediatric patients undergoing laparoscopic surgery who received treatment in Jinhua Maternal and Child Health Hospital from May 2021 to December 2022 were included in this prospective randomized controlled study. These patients were randomly divided into Group A and Group B. Group A ( n = 100) received an intravenous infusion of physiological saline before anesthesia induction, while Group B ( n = 100) received an intravenous infusion of 0.5 μg/kg dexmedetomidine, and the other anesthesia methods were the same as the Group A. Vital signs (mean arterial pressure, heart rate), stress reactions (norepinephrine, cortisol, blood glucose), postoperative recovery status (eye-opening time, time to orientation, extubation time), the occurrence of restlessness (restlessness score, duration of restlessness), and adverse reactions (nausea, vomiting, tachycardia, laryngeal spasm, respiratory depression) were compared between different time points [before infusion (T0), 10 minutes after infusion (T1), postoperative wakefulness (T2), and 5 minutes after extubation (T3)]. Results:At T1, T2, T3, the mean arterial pressure and heart rate in Group B [(81.53 ± 7.45) mmHg (1 mmHg = 0.133 kPa), (78.32 ± 8.23) mmHg, (85.73 ± 7.28) mmHg, (109.43 ± 7.78) beats/minute, (106.22 ± 7.25) beats/minute, and (112.34 ± 6.74) beats/minute] were significantly higher than those in Group A [(76.39 ± 7.21) mmHg, (73.54 ± 7.41) mmHg, (80.34 ± 6.81) mmHg, (102.58 ± 7.34) beats/minute, (99.14 ± 6.90) beats/minute, (107.76 ± 6.38) beats/minute, t = 4.95, 4.31, 5.40, 6.40, 7.07, 4.93, all P < 0.001]. At 1 day after surgery, the levels of norepinephrine, cortisol, and blood glucose in Group B [(352.73 ± 60.32) ng/L, (310.85 ± 67.61) nmol/L, (4.89 ± 0.97) mmol/L ] were significantly lower than those in Group A [(427.82 ± 72.95) ng/L, (375.33 ± 74.97) nmol/L, (5.53 ± 1.10) mmol/L, t = 7.93, 6.38, 4.36, P < 0.001]. The time to eye-opening, time to orientation, and time to extubation in Group B were (10.06 ± 1.93) minutes, (10.54 ± 2.10) minutes, and (11.92 ± 2.06) minutes, respectively, which were significantly shorter than (11.88 ± 2.14) minutes, (12.43 ± 2.65) minutes, and (14.46 ± 2.43) minutes ( t = 6.31, 5.59, 7.97, all P < 0.001). The pediatric anesthesia emergence delirium score in Group B was (8.19 ± 2.10) points, which was significantly lower than (11.56 ± 2.62) points in Group A ( t = 10.03, P < 0.001). The duration of restlessness in Group A was (7.41 ± 1.27) minutes, which was significantly shorter than (9.33 ± 1.65) minutes in Group B ( t = 9.22, P < 0.001). There was no significant difference in the incidence of adverse reactions between Group A and Group B [8.00% (8/100) vs. 6.00% (6/100), χ2 = 0.30, P > 0.05]. Conclusion:Dexmedetomidine has a good application effect in pediatric laparoscopic surgery. It can stabilize the vital signs of children, reduce stress reactions, facilitate postoperative recovery, and reduce restlessness and adverse reactions.
9.Clinical characteristics and prognosis of newly-treated patients with primary central nervous system lymphoma: a multicenter retrospective study
Xinyue LIANG ; Yurong YAN ; Wenrong HUANG ; Wenjia SU ; Shunan QI ; Dabei TANG ; Xuelian LIU ; Qiang GUO ; Lu SUN ; Yunqian LI ; Qingyuan ZHANG ; Fengyan JIN
Journal of Leukemia & Lymphoma 2023;32(8):465-472
Objective:To investigate the clinical characteristics, treatment and prognosis of newly-treated patients with primary central nervous system lymphoma (PCNSL).Methods:Clinical data of 117 newly-treated PCNSL patients who were admitted to the First Hospital of Jilin University, the Fifth Medical Center of Chinese PLA General Hospital, Harbin Medical University Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College from August 2009 to February 2018 were retrospectively analyzed. The patients' age, sex, Eastern Cooperative Oncology Group (ECOG) physical status (PS) score, pathological type, involvement of deep brain tissue, number of lesions, cerebrospinal fluid protein concentration, International Extranodal Lymphoma Study Group (IELSG) score, Memorial Sloan Kettering Cancer Center (MSKCC) score, treatment strategy, and response after the first-line therapy were analyzed using univariate and multivariate Cox proportional hazards models to identify the independent influencing factors for progression-free survival (PFS) and overall survival (OS) of PCNSL patients. Kaplan-Meier method was used for survival analysis.Results:In 117 newly-treated PCNSL patients, 59 cases (50.4%) presented with increased intracranial pressure or focal neurological symptoms at diagnosis; there were 65 cases (55.6%) with single lesions and 52 cases (44.4%) with multiple lesions; 1 patient (0.9%) had lymphoma of T-cell origin, and 116 cases (99.1%) had diffuse large B-cell lymphoma (DLBCL). Among 95 evaluable patients, 41 patients (43.2%) achieved complete remission (CR), 20 patients (21.1%) achieved partial remission (PR), 16 patients (16.8%) achieved stable disease (SD), and 18 patients (18.9%) had progressive disease (PD). In 117 patients with median follow-up of 66.0 months (95% CI 57.9-74.1 months), the median PFS and OS were 17.4 months (95% CI 11.5-23.3 months) and 45.6 months (95% CI 20.1-71.1 months), respectively. The 2-, 3- and 5-year PFS rates were 41.2%, 28.6% and 19.3%, and OS rates were 63.7%, 52.4% and 46.3%, respectively. Univariate Cox regression analysis showed that baseline high-risk MSKCC score group was an adverse prognostic factor for PFS ( P = 0.037), and the first-line chemotherapy with ≥4 cycles of high-dose methotrexate (HDMTX), HDMTX in combination with rituximab, ≥4 cycles of rituximab in combination with HDMTX, and achieving CR or ≥PR after the first-line treatment reduced the risk of disease progression and prolonged the PFS time (all P <0.01); age >60 years old, ECOG-PS score of 2-4 points, elevated cerebrospinal fluid protein concentration, high-risk IELSG score, and high-risk MSKCC score were adverse prognostic factors for OS, and ≥4 cycles of HDMTX and achieving CR or ≥PR after the first-line treatment were favorable factors for OS. Multivariate Cox regression analysis verified that rituximab in combination with HDMTX (yes vs. no: HR = 0.349, 95% CI 0.133-0.912, P = 0.032) and achieving ≥PR after the first-line chemotherapy (yes vs. no: HR = 0.028, 95% CI 0.004-0.195, P < 0.001) were independent favorable factors for PFS; age >60 years old (>60 years old vs. ≤60 years old: HR = 10.878, 95% CI 1.807-65.488, P = 0.009) was independent unfavorable factor for OS, while ≥4 cycles of HDMTX treatment (≥4 cycles vs. <4 cycles: HR = 0.225, 95% CI 0.053-0.947, P = 0.042) was independent favorable factor for OS. Conclusions:The older the PCNSL patients at initial treatment, the worse the prognosis. Intensive and continuous treatment for achieving deeper remission may be the key for improving the outcome of PCNSL patients.
10.Mechanism of Huashi Baidu Prescription in Treating Influenza Viral Pneumonia Based on Transcriptome
Zhongchao SHAN ; Jianhui SUN ; Jianliang LI ; Zeyue YU ; Liyu HAO ; Yurong DENG ; Hairu HUO ; Hongmei LI ; Luqi HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(18):54-61
ObjectiveTo clarify the therapeutic effect of Huashi Baidu prescription on pneumonia in mice caused by influenza A (H1N1) virus and explore its mechanism based on the transcriptome. MethodA mouse influenza viral pneumonia model was built by intranasal infection with influenza A virus, and mice were continuously administered the drug for five days, so as to investigate the general condition, lung index, viral load, pathological morphology of lung tissue, survival time, and prolongation rate of survival time of mice and clarify the therapeutic effect of Huashi Baidu prescription on influenza viral pneumonia. Transcriptome technology was used to detect the differentially expressed genes in the lung tissue of mice in the model group and the normal group, as well as the Huashi Baidu prescription group and the model group, and the potential core target of the Huashi Baidu prescription for the treatment of influenza viral pneumonia was screened. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to verify the effect of Huashi Baidu prescription on the mRNA expression level of core target genes. ResultCompared with the normal group, the lung index and viral load in the lung tissue of the model group were significantly increased (P<0.05, P<0.01). Compared with the model group, the high-dose group of Huashi Baidu prescription significantly prolonged the survival time of mice infected with influenza A virus (P<0.05) and significantly reduced the lung index value of mice (P<0.05) and the viral load of lung tissue. The high-dose, medium-dose, and low-dose groups of Huashi Baidu prescription could significantly reduce lung tissue inflammation, blood stasis, swelling, and other pathological changes in mice (P<0.05, P<0.01). Transcriptome analysis of lung tissue showed that core genes were mainly enriched in the nuclear transcription factor-κB (NF-κB) signaling pathway, interleukin-17 (IL-17) signaling pathway, cytokine-cytokine receptor interaction, and other pathways after the intervention of Huashi Baidu prescription. TRAF6, NFKBIA, CCL2, CCL7, and CXCL2 were the top five node genes with combined score values. Real-time PCR validation showed that Huashi Baidu prescription significantly downregulated the mRNA expression of key genes TRAF6 and NFKBIA in the NF-κB signaling pathway, as well as chemokines CCL2, CCL7, and CXCL2 (P<0.05, P<0.01). ConclusionHuashi Baidu prescription has a therapeutic effect on influenza viral pneumonia, possibly by inhibiting the expression of key nodes TRAF6 and NFKBIA in the NF-κB signaling pathway and that of chemokines CCL2, CCL7, and CXCL2, reducing the recruitment of inflammatory cells and viral load, and exerting anti-influenza viral pneumonia effects.

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