1.Preparation of 4-sulfonylcalix6arene-modified cotton for uranium contamination removal
Haoxin GUO ; Yilong WANG ; Zebao ZHENG ; Kunlu LIU ; Rongqing HUANG ; Zhibing ZHENG ; Bo HUANG ; Zhixin WANG ; Meiyu WANG ; Benbo LIU ; Guo CHEN ; Xu WANG ; Zhihua YANG ; Maoxiang ZHU
Chinese Journal of Radiological Health 2023;32(6):603-610
Objective To prepare 4-sulfonylcalix[6]arene-modified cotton fibers for adsorption and removal of uranium based on the specific complexation of calix[6]arene with uranium (VI). Methods Chemical grafting was used for the modification of cotton, which reacted with α-bromoisobutyryl bromide, glycidyl methacrylate, and 4-sulfonylcalix[6]arene. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FTIR) were used to characterize the structure of 4-sulfonylcalix[6]arene-modified cotton (Cotton S-C[6]a). A Franz diffusion cell was used to simulate uranium-contaminated skin. Laser fluorimetry was used to determine the uranium content. Results SEM, XPS, and FTIR showed that cotton fibers were successfully grafted with 4-sulfonylcalix[6]arene. The optimal conditions of Cotton S-C[6]a for the adsorption of uranium (VI) was pH 4.0, duration of 20 min, and 20 mg of adsorbent. The adsorption process fitted well with pseudo-secondary-order kinetics. The uranium removal efficiency of Cotton S-C[6]a was up to 78.46% in aqueous solution and 81.72% on skin. Conclusion The synthesized Cotton S-C[6]a is highly efficient in the removal of uranium (VI) in solution and on contaminated skin.
2.Discovery of novel exceptionally potent and orally active c-MET PROTACs for the treatment of tumors with MET alterations.
Pengyun LI ; Changkai JIA ; Zhiya FAN ; Xiaotong HU ; Wenjuan ZHANG ; Ke LIU ; Shiyang SUN ; Haoxin GUO ; Ning YANG ; Maoxiang ZHU ; Xiaomei ZHUANG ; Junhai XIAO ; Zhibing ZHENG ; Song LI
Acta Pharmaceutica Sinica B 2023;13(6):2715-2735
Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC50 values and achieved picomolar DC50 values and >99% of maximum degradation (Dmax) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-METY1230H and c-METD1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.
3.The clinical significance of globus pallidus MRI signal intensity in the early identification of neonatal bilirubin encephalopathy
Gang LIU ; Huabao PENG ; Zhibing XIAO ; Shiteng HU ; Qiongmei TANG ; Yang CAO ; Yanfeng OUYANG
Chinese Journal of Neonatology 2020;35(1):10-15
Objective To study the clinical significance of globus pallidus signal intensity and the intensity ratio of globus pallidus and putamen (G/P ratio) on magnetic resonance T1WI for the early recognition of neonatal bilirubin encephalopathy.Method From January to December 2017,full-term neonates with hyperbilirubinemia admitted to the neonatology department of our hospital were enrolled in the case group,and full-term neonates without hyperbilirubinemia in the control group.The clinical data,globus pallidus T1WI signal intensity,G/P ratio and the follow-up data were collected.According to the level of hyperbilirubinemia,the neonates in the case group were further assigned into mild hyperbilirubinemia group (serum bilirubin:222 to <256 μmol/L),moderate hyperbilirubinemia group (serum bilirubin:256 to <342 μmol/L),and severe hyperbilirubinemia group (serum bilirubin:≥ 342 μmol/L).According to the injury score of ABE,the neonates with ABE were assigned into mild ABE group,moderate ABE group and severe ABE group.The correlation of globus pallidus T1WI and T2WI signal values,G/P ratio and the serum bilirubin level and ABE degree were analyzed;receiver operating characteristic (ROC) curve was drawn to explore the predictive value of the T1WI signal value and G/P ratio for the diagnosis of ABE;the changes of globus pallidus T1WI and T2WI signal values during the first 6 months after birth and the results of follow-up to 1 year after discharge were also analyzed.Result A total of 175 neonates were included in the case group (65 in the mild hyperbilirubinemia group,71 in the moderate hyperbilirubinemia group and 39 in the severe hyperbilirubinemia group) and 43 neonates in the control group.39 neonates were diagnosed as ABE (21 mild ABE,12 moderate ABE,and 6 severe ABE).The first T1WI signal value and G/P ratio of neonates in the severe hyperbilirubinemia group was higher than the moderate hyperbilirubinemia group,the mild hyperbilirubinemia group and the control group;the T1WI signal value and G/P ratio in the moderate hyperbilirubinemia group was higher than the mild hyperbilirubinemia group and the control group (P < 0.05).No significant difference existed between the mild group and the control group(P > 0.05).T2WI values showed no differences among neonates with different bilirubin levels (P > 0.05).The first T1WI signal value and G/P ratio in the severe ABE group were significantly higher than the moderate and mild ABE group,and the moderate ABE group higher than the mild ABE group (P < 0.05).The ROC curve indicated the optimal cut-off value of T1WI signal and G/P ratio were 628 and 1.38,respectively.Among all the 175 neonates,9 had a decrease in T1WI signal value and an increase in T2WI signal value at 6 months after birth.After 1 year of follow-up visits,7 children were finally diagnosed as chronic bilirubin encephalopathy.All these children had increased signal intensity on T1WI in the acute phase,plus a decreased T1WI signal and an increased T2WI signal in 1 ~ 6 months after birth.Conclusion The globus pallidus T1WI signal and G/P ratio are closely related to the serum bilirubin level and ABE severity.If T1WI signal value > 628 or G/P value > 1.38,ABE should be considered.The T1WI signal value and G/P ratio play important roles as indicators for the early recognition of neonatal bilirubin encephalopathy.
4.Ultrasound-guided transversus abdominis plane block for elderly herpetic neuralgia located in anterior abdominal wall:a randomized and controlled trial
Zhibing PI ; Xuzhong XU ; Hai LIN ; Jianping YANG
Chinese Journal of Geriatrics 2019;38(5):561-564
Objective To evaluate the efficacy of ultrasound guided transversus abdominis plane block for elderly herpetic neuralgia located in anterior abdominal wall.Methods A total of 112 elderly patients aged 65-75 years with less than 30 days of herpes zoster neuralgia located in anterior abdominal wall were enrolled for receiving a treatment of transversus abdominis plane block.Patients were randomly allocated into two groups:the control group (n =56) taking gabapentin and celebrex,and the observation group (n =56)receiving transversus abdominis plane block (three times per week for two weeks) as add on therapy to gabapentin and celebrex.Morphine 10 mg was ready for oral application in breakthrough pain.Pain was evaluated by McGill scores assessed by short-form of Mcgill pain questionnaire(SF-M PQ)and visual analogue scale(VAS)before(T0)and after 1 (T1)and 2 weeks(T2)of transversus abdominis plane block,and 1 (T3)and 8(T4)weeks after end of the treatment.Pain relief(PAR)was calculated by the formula:PAR=(VAS score before block-VAS score after block)/ VAS score before block × 100%.The morphine consumption and sleep quality were observed during the treatment and 1 week after treatment.Analgesic efficacy was graded 8 weeks after end of treatment.The effective rate and good response rate were calculated.Incidences of complications were recorded.Results There was no significant difference in the VAS score between the two groups before treatment(t =0.419,P >0.05),while VAS scores after treatment were lower in the observation group than in the control group(t =17.925,19.662,12.580 and 13.987,respectively,P<0.05).Before treatment,there was no significant difference in the total score of McGill between the two groups(t =0.544,P>0.05).After treatment,the total scores of McGill were lower in the observation group than in the control group(t =18.612,20.135,13.213 and 12.356,respectively,P <0.05).The pre-therapy scores of sleep quality after treatment were decreased in the observation group as compared with the control group(t =7.798,9.545,10.335 and 16.318,respectively,P <0.05).Before treatment and at different time points of T1,T2,T3,T4,the morphine consumptions were not significant different between two groups(t =1.939,P>0.05).While after treatment,the morphine consumptions were decreased in the observation group versus in the control group(t =22.341,16.758,17.827,15.541 respectively,P <0.05).No punctures of abdominal cavity,chest cavity,internal organs or blood vessels by mistake occurred.Conclusions Ultrasound-guided transversus abdominis plane block is effective and has less adverse reactions in treating herpetic neuralgia located in anterior abdominal wall.
5.Bactericidal effect of ozonated camellia oil on Staphylococcus aureus in vitro
Yaping XIANG ; Jianyun LU ; Feifeng LI ; Jian HUANG ; Caifeng YANG ; Zhibing FU ; Lihua GAO
Journal of Central South University(Medical Sciences) 2018;43(2):139-142
Objective:To explore a new method for detecting the bactericidal effect of oiling agent in vitro,and to determine the disinfectant effecacy ofozonated camellia oil on Staphylococcus aureus.Methods:Suspension of Staphylococcus aureus was prepared and innoculated on the LB plate by plate scribing method.After culture overnight,21 bacterial monoclones with the same diameter were selected and divided into 3 groups:A negative control group,a baseoil (camellia oil) group and an ozonated camellia oil group.We used a ring to isolate the single clone and added oil inside the ring,cultured the whole plate over night,picked out each single clone (with gel) to 5 mL LB medium and cultured it for 12 h.The final concentration of the LB medium was detected by plate count method and turbidimetry.Results:According to the plate count method and turbidimetry,the bacterial concentration in the ozonated camellia oil group was lower than that in the negative control group and base oil group Conclusion:Bacterial monoclone culture method shows that ozonated camellia oil can significantly kill Staphylococcus aureus,and this method is an effective method for evaluating the bactericidal function of the oiling agent in vitro.
6.Meta-analysis of Angong Niuhuang Pill Combined with Chemical Drug in the Treatment of Severe Craniocerebral Injury and Its Effect on Patient's Mg2+ Concentration in Peripheral Blood
Huai TU ; Haojun PENG ; Jicai LAI ; Guozhen YU ; Xiaomei YANG ; Zhibing WU ; Zhenglun ZENG
China Pharmacy 2018;29(1):121-124
OBJECTIVE:To evaluate clinical efficacy of Angong niuhuang pill combined with chemical drug in the treatment of severe craniocerebral injury and its effect on the concentration of Mg2+ in peripheral blood,and to provide evidence-based reference in clinic.METHODS:Retrieved from Chinese Journal Full-text Database,China Science and Technology Journal Database,China Bxdxiology Medicine disc,Wanfang Database,Chinese Clinical Trial Registry,PubMed,Excerpta Media Database,The Cochrane Library,Web of Science,Clinical Trials,and related literatures of intemet searched by Google Scholar,randomized controlled trials (RCT) about Angong niuhuang pill combined with chemical drug (trial group) vs.chemical drug (control group) in the treatment of severe craniocerebral injury and its effects on the concentration of Mg2+ in peripheral blood were collected.After literature screening,data extraction,quality evaluation with modified Jadad scale,meta-analysis of Glasgow Coma Scale (GCS) scores and Mg2+ concentration in peripheral blood were conducted by using Rev Man 5.3 statistical software after 7 d of treatment.RESULTS:A total of 6 RCTs were included,involving 773 patients.Results of meta-analysis showed that GCS [MD=2.87,95%CI (1.64,4.10),P<0.01] and Mg2+ concentration in peripheral blood [MD=0.11,95%CI(0.06,0.16),P<0.01] of trial group were significantly higher than those of control group,with statistical significance.CONCLUSIONS:Therapeutic efficacy of Angong niuhuang pill combined with chemical drug is better than that of chemical drug alone in the treatment of severe craniocerebral injury,can improve clinical symptom and prognosis.
7.Comparative Study on Three Open Access Drug Label Databases: Drugs@FDA, FDA Online Label Repository and DailyMed
Qi SUN ; Jiying HAO ; Juntao MA ; Zhibing YANG
China Pharmacy 2018;29(1):131-134
OBJECTIVE:To provide reference for pharmacy staff to choose different drug label databases according to different needs.METHODS:The information organization mode of the three open access drug label databases that included Drugs@FDA,FDA Online Label Repository and DailyMed had been collected and analyzed comparatively from three aspects:retrieval function settings,search results display,data resources and service targets.RESULTS & CONCLUSIONS:In respect of retrieval function,DailyMed provided the most abundant retrieval functions than others.In respects of search results display,DailyMed provided the highest degree of formatted data,followed by FDA Online Label Repository,while Drugs@FDA provided semi-formatted data.Three databases provided the functions of page replication and printing,among which the interface of DailyMed was friendlier and the content of DailyMed was more open;it provided all the download functions.In respects of data resources and service targets,developers of Drugs@FDA and FDA Online Label Repository were FDA,and that of DailyMed was National Library of Medicine (NLM).The data sources used by Drugs@FDA were the drug labels after strict approval by FDA,and the description of drug information by Drugs@FDA was the most comprehensive.FDA Online Label Repository was the original drug labels submitted by the manufacturer to FDA,which was the latest content,and even included unlisted drugs.The data sources of DailyMed were from the information listed on the drug package,and included the information of drug label which was listed but not approved strictly;it covered most comprehensive drugs.
8.Suppression of epipolythiodioxopiperazine compound C87 on growth of tumor cells and its effect on production of reactive oxygen species
Yiyang GAO ; Xiaoli WEL ; Xiaowen YANG ; Fengxia REN ; Jianquan ZHENG ; Zhibing ZHENG ; Ruibin SU
Chinese Journal of Pharmacology and Toxicology 2015;(2):253-259
OBJECTIVE To study the effect of epipolythiodioxopiperazine compound C87 on tumor cell proliferation and explore the potential mechanisms. METHODS Tumor cells were exposed to C87 0.05-1 μmol.L-1 for 24, 48 and 72 h, cell viability was determined by sulforhodamine B (SRB) assay and the half growth inhibition (Gl50 ) was calculated. After treatment with C87 0.1-2.5 μmol.L-1 for 6 h, or C87 2.5 μmol.L-1 for 0-6 h, the generation of reactive oxygen species (ROS) was measured using the compound 2′,7′-dichlorofluoresceindiacetate and flow cytometry analysis. After treatment with C87 2.5 μmol.L-1 , either alone or with antioxidant N-acetylcysteine (NAC), for 6 h, the generation of ROS was measured by flow cytometry analysis. Tumor cells were exposed to C87 0.05-1 μmol.L-1 , either alone or with NAC, for 24 and 48 h, while cell viability was determined by SRB assay. RESULTS The cell viability was significantly reduced following exposure to C87 0.05-1 μmol.L-1 for 24, 48 and 72 h in a concentration-dependent manner in A549, HCT116, HeLa and SMMC7721 cells(P<0.05). At 72 h, the value of r2 was 0.946, 0.989, 0.973 and 0.984(P<0.05), respectively. The cell viability was significantly reduced following exposure to C87 1 μmol.L-1 for 24 - 72 h in a time-dependent manner in A549, HCT116, HeLa and SMMC7721 cells(P<0.05). The value of r2 was 0.983, 0.956, 0.951 and 0.873(P<0.05), respectively. The generation of ROS was increased after exposure to C87 0.25-2.5 μmol.L-1 in a concentration-dependent manner in HCT116 and HeLa cells for 6 h (r2 = 0.760, P = 0.045: r2 = 0.987, P=0.001), and after exposure to C87 2.5 μmol.L-1 in a time-dependent manner in HCT116 and HeLa cells for 0.5-6 h (r2 = 0.886, P = 0.017: r2 = 0.994, P = 0.000).The C87-induced ROS generation could be blocked by NAC in HCT116 and HeLa cells(P<0.05). The C87 induced cell death could be blocked by NAC 5 and 10 mmol.L-1 , and the Gl50 value was 1.446 and 1.134 μmol.L-1 for 24 h (the Gl50 value of C87 group was 0.513 μmol.L-1 ), and 0.882 and 1.166 μmol.L-1 for 48 h (the Gl50 value of C87 group was 0.333 μmol.L-1 ). CONCLUSION The novel epipolythiodioxopiperazine derivative C87 exerts potent antitumor activity in vitro, possibly via triggering ROS production.
9.Reactivation of nanoparticulated HI-6 on acetylcholinesterase activity in soman poisoned mice
Feijian WANG ; Jun YANG ; Feng CHENG ; Wanhua LI ; Zhiyong NIE ; Yuan LUO ; Xin SUI ; Zhao WEI ; Zhibing ZHENG ; Yongan WANG ; Tongyu FANG
Chinese Journal of Pharmacology and Toxicology 2014;(2):255-261
OBJECTIVE Based on different drug loading models,three types of nanoparticulated HI-6 were prepared and their reactivations on inhibited acetylcholinesterase (AChE)in peripheral and central nervous syste ms were evaluated and compared in so man-intoxicated mice.METHODS Three kinds of nano-reactivators including HI-6 loaded human serum albunin nanoparticle (HSA-HI-6 NP),HI-6 absorptive mesoporous silica nanoparticle(MSN-HI-6),polylactico-glycolic acid nanoparticle coated HI-6 (PLGA-HI-6 NP)were prepared.The characteristic of all blank nanocarriers was observed through elec-tron microscope.HI-6 release rate of nano-reactivators was also determined in vitro.Then the reactiva-tion rate of nano-reactivators at a constant HI-6 dosage(22 mg·kg -1 )on so man-inhabited AChE both in blood and brain was assessed the so man intoxicated mice(120 μg·kg -1 ,sc).RESULTS All the syn-thetic nanocarriers met the de mand for nanodrug use in vivo.The rate of HI-6 release of nano-reactiva-tors was HI-6 >HSA-HI-6 NPs >MSN-HI-6 >PLGA-HI-6 NP in vitro.On the reactivations of so man-inhibited mice blood AChE,the free HI-6 and HSA-HI-6 NPs,as well as MSN-HI-6 showed co mparable reactivation rates(20% -30%)but were greater than that of PLGA-HI-6 NPs (6.2%)(P <0.01 ). However on the reactivations of so man-inhibited mice brain AChE,the reactivation rate of HSA-HI-6 NP (15.3%)was significantly higher than that of PLGA-HI-6 NP(3.3%)and free HI-6(6.3)(P<0.01 ).In addition,MSN-HI-6 group had a significant reactivation rate compared to PLGA-HI-6 NPs(P <0.01 ). But there was no statistic difference between MSN-HI-6 and free HI-6.CONCLUSION The reactivation potency changed obviously with different drug loading models and HSA-HI-6 NPs had the most potent reactivation on so man-inhibited AChE in both blood and brain.
10.Reliability and validity of stress vulnerability prediction scale in soldiers
Jieqiong GUO ; Zhibing YANG ; Xia ZHU
Chinese Journal of Behavioral Medicine and Brain Science 2013;(1):72-74
Objective To develop stress vulnerability prediction scale for soldiers.Methods 148 items were determined by reviewing items in relating literatures and scales,interview,panel discussion and expert consultation.Then 431 and 351 soldiers in two times were picked out randomly as samples from Army Northwest District.Item analysis,exploratory factor analysis,reliability analysis and confirmatory factor analysis were used to analyse the data.Results Stress vulnerability prediction scale comprised five subscales:traumatic events,positive affect,negative trait,negative coping and interpersonal support.The scale was comprised of 59 items,and the factor loading of the items ranged from 0.503 to 0.839.Cronbach's α coefficient of the five subscales were 0.777,0.903,0.923,0.882,0.908,and the Cronbach's α coefficient of the scale was 0.895.Confirmatory factor analysis showed a higher goodness of fit(RESEA =0.058,NFI =0.89,NNFI =0.93,CFI =0.94,IFI =0.98).Conclusion Stress vulnerability prediction scale in soldiers has good psychometric properties,and can be used as a prediction measurement tool for measuring the stress disorder for soldiers.

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