1.Diagnosis and treatment of chronic cough with combined cause-oriented diagnostic process and empirical therapy
Feng WU ; Haigui WU ; Sifang WU ; Bida CHEN ; Wutie ZHOU ; Weiming LIN
Clinical Medicine of China 2012;28(6):607-609
Objective To understand the frequency distribution of causes to facilitate the diagnosis and treatment of chronic cough.Methods Patients were recruited according to the inclusion criteria:chronic cough more than 8 weeks;normal X-ray appearance;coughing symptoms as the main or only symptom.Disease history was referred and physical examination was conducted,according to the diagnosis criteria of chronic cough causeoriented processes.If laboratory examination results are missing for a patient,empirical treatment will be combined as a treatment for this patient.Finally,the curative effect and the cause of disease will be analyzed.Results Seventy-nine patients were followed up.Twenty-eight,12,22,10,and 7 patients respectively were suspected of having CVA,EB,UACS,AC and GERC,among whom,23,9,14,9 and 4 were confirmed for their diagnosis,and 84.1%,75.0%,63.6%,90.0%,and 57.1% of them received effective targeted therapies,accounting for 29.1%,11.4%,24.1%,11.4%,and 6.3% respectively of all patients.The overall response rate was 74.7%.Conclusion The diagnosis and treatment of chronic cough with combinational cause-oriented diagnostic process and empirical therapy produce high effective rate with low cost.In addition,it could help understand the local frequency distribution of causes of chronic cough.It may be worth wide clinical application.
2.Expression and clinical significance of induced sputum neutrophil S100 A8/A9 in children with bronchial asthma
Sifang ZHOU ; Yingping DING ; Xinlong WU ; Jian SUN ; Xiangyun HU ; Huan DENG
Tianjin Medical Journal 2017;45(3):267-270
Objective To investigate the expression and clinical significance of neutrophil S100A8/A9 in induced sputum in children with bronchial asthma. Methods A total of 108 cases of bronchial asthma patients in the FourthAffiliated Hospital of Nanchang University were involved in the study form October 2014 to October 2015. According to the severity of the disease, the patients were divided into mild group (n=40), moderate group (n=36) and severe group (n=32). Twenty health children were taken as control group at the same period. All the patients were treated with budesonide aerosol for three months, and the control group was received aerosol inhalation for normal saline (NS). The ratio of forced expiratory volume in one second and forced vital capacity (FEV1/FVC, FEV1%) were used to evaluate the pulmonary function in two groups. The asthma control questionnaire (AcQ-5) score was used to estimate the asthma control effects. The expression level of neutrophil S100A8/A9 mRNA in induced sputum was detected by real-time PCR. The correlation of S100A8/A9 mRNA, AcQ-5 score and FEV1%was analyzed. Results Before the treatment, the FEV1%decreased, while the AcQ-5 score and express level of S100A8/A9 mRNA significantly increased with the severity of disease (all P<0.01). Three months after treatment, asthma was completely controlled in 60 patients, partial controlled in 31 cases and uncontrolled in 17 cases. With the improvement of the therapeutic efficacy, the FEV1%significantly decreased, while the express level of S100A8/A9 mRNA significantly increased (all P < 0.01). The express level of S100A8/A9 mRNA in induced sputum neutrophils was negatively correlated with FEV1%(r=-0.327 and-0.406 respectively, P<0.05), which was positively correlated with ACQ-5 score (r=0.704 and 0.817, P<0.05). Conclusion The level of S100A8/A9 expression in induced sputum neutrophil is positively correlated with the severity of asthma, which can be used as clinical indicators of the severity and the efficacy of asthma.
3.Separation and Identification of Chemical Components in Ethyl Acetate Fraction and Water Fraction from Tripterygium wilfordii
Ruikun YANG ; Sifang WU ; Jun YAN ; Jicheng SHU ; Rui ZHANG ; Shenglin ZHANG ; Tianyou CAO ; Jianqun LIU
China Pharmacy 2019;30(5):638-641
OBJECTIVE: To separate and identify chemical components in ethyl acetate fraction and water fraction from Tripterygium wilfordii, and to provider basis for further pharmacological study. METHODS: The ethyl acetate fraction and water fraction from T. wilfordii were separated and purified by MCI GEL-CHP 20P column chromatography, C18 RP silica gel column chromatography, Sephadex LH-20 gel column chromatography and HPLC. The structures of compounds were analyzed and identified by 1H-NMR, 13C-NMR and physicochemical properties. RESULTS: Two compounds were isolated from ethyl acetate fraction of T. wilfordii, namely orthosphenic acid (compound 1), dibutylphthalate (compound 2). Eight glucosides were isolated from water extract of T. wilfordii, namely 2,6-dimethoxy-4-hydroxymethyl-phenyl-1-O-beta-D-glucopyranoside (compound 3), 2,6-dimethoxy-4-hydroxyphenol-1-O-β-D-glucoside(compound 4), 4-hydroxy-1-(2-hydroxyethyl)-phenyl-3-O-β-D-glucopyranoside (compound 5), 3,4-dimethoxy-phenyl-1-O-β-D-glucopyranoside (compound 6),β-adenosine (compound 7), ligustrin (compound 8), epicatechin-8-C-β-D-galactoside (compound 9) and 2-hydroxynaringenin-7-O-β-glucoside (compound 10). CONCLUSIONS: Chemical components of ethyl acetate fraction and water fraction are separated and identified from T. wilfordii.
4.Identification of a novel PHGDH covalent inhibitor by chemical proteomics and phenotypic profiling.
Chen CHEN ; Tianyu ZHU ; Xiaoqin LIU ; Dongrong ZHU ; Yi ZHANG ; Sifang WU ; Chao HAN ; Hao ZHANG ; Jianguang LUO ; Lingyi KONG
Acta Pharmaceutica Sinica B 2022;12(1):246-261
The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH.