1.Development and prospects of predicting drug polymorphs technology
Mei GUO ; Wen-xing DING ; Bo PENG ; Jin-feng LIU ; Yi-fei SU ; Bin ZHU ; Guo-bin REN
Acta Pharmaceutica Sinica 2024;59(1):76-83
Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.
2.Effect of safflower yellow pigment injection combined with alprostadil on patients after coronary artery bypass grafting
Xin-Hua ZHANG ; Chun-Mei REN ; Li-Jie JIANG ; Wei-Guang YANG ; Hong-Ling SU ; Jing-Yu ZHAO
Chinese Journal of cardiovascular Rehabilitation Medicine 2024;33(5):590-593
Objective:To investigate the effect of safflower yellow pigment injection combined with alprostadil on patients after coronary artery bypass grafting(CABG).Methods:A total of 92 patients with coronary heart disease who received CABG in Department of Cardiovascular Surgery,Handan Central Hospital between September 2018 and September 2020 were selected.According to order of admission,they were divided into control group(n=46,from September 2018 to Sep-tember 2019,routine therapy+alprostadil after CABG)and study group(n=46,from October 2019 to September 2020,safflower yellow pigment injection based on control group),both groups were treated for 28d.On 3d after drug withdraw-al,therapeutic effect,cardiac function indexes,four myocardial enzyme spectrum and perioperative indexes were compared between two groups.Results:On 3d after drug withdrawal,compared with control group,patients in study group had sig-nificant higher total effective rate(73.9%vs.91.3%),left ventricular ejection fraction(LVEF)[(55.77±4.48)%vs.(62.18±4.21)%](P=0.028,<0.001),and significant lower left atrial diameter(LAD)[(36.83±3.45)mm vs.(32.09±3.23)mm],left ventricular end-diastolic diameter(LVEDd)[(49.04±4.65)mm vs.(43.83±5.24)mm],levels of creatine kinase(CK)[(125.13±14.21)U/L vs.(62.56±8.42)U/L],lactate dehydrogenase(LDH)[(203.58±31.63)U/L vs.(156.07±22.26)U/L],aspartate aminotransferase(AST)[(44.25±12.98)U/L vs.(35.41±12.37)U/L]and creatine kinase isoenzyme MB(CK-MB)[(28.11±9.84)U/L vs.(17.59±7.41)U/L](P<0.001 all).Conclusion:The combination of safflower yellow pigment injection and alprostadil can improve the thera-peutic effect and heart function,and reduce myocardial injury in patients after CABG.
3.Construction of nursing pathway and clinical application of an early warning scoring model for elderly patients with acute heart failure based on a modified emergency severity index
Shirong YANG ; Jiang WANG ; Xiuping WANG ; Xiaochi REN ; Mei SU ; Di WEN ; Lan CHEN ; Zhu ZHU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2023;30(6):730-734
Objective To enhance the triage efficiency of patients with acute heart failure(AHF)by improving emergency severity index(ESI)score,and to achieve stratified care for patients with AHF.Additionally,the aim is to improve the combination of stratified scores and nursing care in emergency departments to address the limitations of current studies.Methods A retrospective nested cohort study was conducted on 120 patients with AHF admitted to the Affiliated Hospital of Guizhou Medical University from January 1,2019 to December 30,2021.According to the clinical outcomes of the patients,the patients were divided into subgroup A(71 cases,recovered after treatment,no serious complications during treatment),subgroup B[35 cases,discharged after treatment,multiple organ dysfunction syndrome(MODS),acute respiratory distress syndrome(ARDS),shock and other serious complications occurred during treatment],and subgroup C(14 cases,cardiac death during treatment).A prospective randomized controlled study involving 106 patients with AHF admitted to our hospital from January 1 to December 30,2022,was conducted,and the patients were divided into control group(53 cases)and stratified care group(53 cases)according to the random number table method.The control group received routine nursing care,while patients in the stratified care group received stratified care based on the ESI scoring clinical care pathway.The early warning score model of elderly patients with AHF was constructed with risk threshold as warning signal.The improved ESI scoring criteria were used to score AHF patients,with a total score of 25 points.The higher the score,the higher the risk.0-10 is divided into Ⅰ level risk,>10-20 is divided into Ⅱ level risk,>20 is divided into Ⅲ level risk.Implement nuring at grades Ⅲ,Ⅱ,and Ⅰ,respectively.The changes of modified ESI scores in subgroup A,subgroup B and subgroup C were observed,and Spearman correlation coefficient was used to evaluate the correlation between modified ESI scores and clinical outcomes of different severity of disease.Receiver operator characteristic curve(ROC curve)was drawn to evaluate the effectiveness of the risk threshold classification method of different nursing plan designs in the stratified nursing group and the control group,and to compare the efficiency differences of emergency nursing rescue time,rescue success rate,and stay time in the emergency department,and the incidence of complications such as MODS,ARDS,shock and nursing satisfaction during treatment between the stratified nursing group and the control group.Results The modified ESI score in subgroup C was the highest,significantly higher than that in subgroup B and A(19.6±1.7 vs.17.8±1.5,15.3±1.3,all P<0.05).Spearman correlation analysis showed that the modified ESI score was significantly positively correlated with the occurrence of complications,the occurrence of cardiac death,and the recovery after treatment(r values were 0.623,0.635,0.322,P values were 0.004,0.003,0.012,respectively).Therefore,an improved ESI score has a certain early warning effect on complications and cardiac death of patients.ROC curve analysis showed that the area under the ROC curve(AUC)of routine care for stratified care was 0.710 and 0.620,and the 95% confidence interval(95% CI)was 0.620-0.750 and 0.580-0.690,respectively,with Pvalues of 0.023 and 0.034.It shows that the difference between the two nursing methods is significant,and further indicates that the risk threshold classification method designed in this study is effective.With the increase of risk,the rescue time and emergency stay time of the two groups were gradually extended,and the success rate of rescue was gradually decreased,the rescue time and emergency stay time of grade Ⅲ risk were the longest and the success rate of rescue was the lowest,and the rescue time and emergency stay time of the stratified nursing group were significantly shorter than those of the control group(minutes:59.6±6.3 vs.76.5±7.2 and 57.6±5.4 vs.68.2±7.1,both P<0.05),the success rate of rescue was significantly increased[(68.7±6.1)% vs.(54.6±5.2)%,P<0.05],and the difference of rescue time between grade Ⅰ risk and grade Ⅲ risk was the largest.There were significant differences in the success rate of rescue and the duration of emergency stay in grade Ⅲ risk.The incidence of complications such as MODS,ARDS and shock in stratified care group was significantly lower than that in control group[incidence of MODS:13.2%(7/53)vs.18.9%(10/53),incidence of ARDS:15.1%(8/53)vs.22.6%(12/53),incidence of shock:13.2%(7/53)vs.20.8%(11/53),all P<0.05],satisfaction of patients with service attitude,operation technique,comfort and timeliness were significantly improved compared with the control group[service attitude:28.3%(15/53)vs.18.9%(10/53),operation technology:30.2%(16/53)vs.20.8%(11/53),comfort:32.1%(17/53)vs.24.5%(13/53),timeliness:32.1%(17/53)vs.24.5%(13/53),all P<0.05].Conclusion Based on the modified ESI score,early risk warning thresholds are divided and stratified nursing is conducted,which is beneficial for timely intervention in AHF,effectively ensuring the clinical nursing value of patients during the implementation of medical measures,and has broad application prospects.
4.Pharmacological Analysis of Xuanfei Huazhuo Prescription in Treatment of Coronavirus Disease-2019
Dong-ling LIU ; Hao-jia WANG ; Wei-yu REN ; Jing SU ; Yi-jun ZHENG ; Wen-qian HOU ; Xiao-jie JIN ; Yan-mei NING ; Jia-wei LI ; Zhi-ming ZHANG ; Yong-qi LIU
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(16):40-49
Objective:The targets and signaling pathways of Xuanfei Huazhuo prescription (XFHZP) for the treatment of coronavirus disease-2019 (COVID-19) were explored, and its possible action mechanisms were described through network pharmacology and basic analysis of modern pharmacology. Method:The compounds and targets in XFHZP were collected through TCMSP and BATMAN-TCM databases. The targets of COVID-19 were studied by GeneCards, NCBI and CTD databases. The PPI network was constructed through STRING database. The networks of "herb-meridian" and "traditional Chinese medicines-compounds-targets-disease" were generated by Cytoscape 3.7.0. Then, Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis and Gene Ontology(GO) analysis were made for shared targets through the Omicshare platform. In addition, the disease targets of multiple organ injury, immune injury and severe acute respiratory syndrome (SARS) were retrieved and then mapped with XFHZP. The ratio of intersection targets to XFHZP's targets was calculated. Result:XFHZP has 10 traditional Chinese medicines in total, including 6 medicines with the meridian tropism to lung, 5 medicines with the meridian tropism to the spleen and 5 medicines with the meridian tropism to the stomach. There were 409 compounds and 2 271 targets. There were 8 same inflammatory factors in targets between XFHZP and COVID-19, and each inflammatory factor corresponded to multiple compounds. XFHZP and COVID-19 had 135 intersection targets, and 36 key targets were screened out. A total of 172 signaling pathways were screened out through KEGG signal pathway enrichment (
5.Screening and identification of GABA-producing microbes in fermentation process of Sojae Semen Praeparatum.
Jing-Jing XIONG ; Jia-Xiu REN ; Shu-Han ZHOU ; Ming-Sheng SU ; Li-Yuan WANG ; Mei-Zhi WENG ; Wei-Hua XIE ; Xiao-Mei XIE
China Journal of Chinese Materia Medica 2019;44(11):2266-2273
A high-content GABA was found in Sojae Semen Praeparatum(SSP), which is a famous traditional Chinese medicine and officially listed in Chinese Pharmacopoeia. To screen out and identify GABA-producing microbes from samples at different time points during the fermenting process of SSP, traditional microbiological methods combined with molecular biological methods were used to study the predominant GABA-producing microorganisms existing in the fermenting process of SSP. This study would lay a foundation for further studying the processing mechanism of SSP. The fermenting process of SSP was based on Chinese Pharmacopoeia(2010 edition), and samples were taken at different time points during the fermenting process of SSP. The bacteria and fungi from samples at different time points in the fermenting process of SSP were cultured, isolated and purified by selective medium, and dominant strains were selected. The dominant bacteria were cultured in the designated liquid medium to prepare the fermentation broths, and GABA in the fermentation broth was qualitatively screened out by thin-layer chromatography. The microbial fermentation broth with GABA spots in the primary screening was quantitatively detected by online pre-column derivatization and high performance liquid chromatography established in our laboratory. GABA-producing microorganisms were screened out from predominant strains, and their GABA contents in fermentation broth were determined. The DNA sequences of GABA-producing bacteria and fungi were amplified using 16S rDNA and 18S rDNA sequences by PCR respectively. The amplified products were sequenced, and the sequencing results were identified through NCBI homology comparison. Molecular biological identification was made by phylogenetic tree constructed by MEGA 7.0 software. Through the homology comparison of NCBI and the construction of phylogenetic tree by MEGA 7.0 software, nine GABA-producing microorganisms were screened out and identified in this study. They were Bacillus subtilis, Enterococcus faecium, E. avium, Aspergillus tamarii, A. flavus, A. niger, Cladosporium tenuissimum, Penicillium citrinum and Phanerochaete sordida respectively. For the first time, nine GABA-producing microorganisms were screened out and identified in the samples at different time points during the fermenting process of SSP in this study. The results indicated that multiple predominant GABA-producing microorganisms exist in the fermenting process of SSP and may play an important role in the formation of GABA.
Bacteria
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classification
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metabolism
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Chromatography, High Pressure Liquid
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Fermentation
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Fungi
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classification
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metabolism
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Phylogeny
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Seeds
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microbiology
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Soybeans
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microbiology
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gamma-Aminobutyric Acid
;
biosynthesis
6.Development of a 30 Y-STR Loci with middle or low mutations multiplex PCR system
Weiwei WU ; Honglei HAO ; Huaifeng WANG ; Bing LIU ; Xinglin MEI ; Xiang ZHOU ; Yanjia SU ; Wenyan REN ; Yanfang FU ; Xiaoting ZHENG ; Dejian LV
Chinese Journal of Forensic Medicine 2018;33(1):11-16
Objective To deveplope construct and validate a novel multiplex PCR system comprised of 30 Y-STR markers only with low and moderate mutation rates. Methods 30 Y-STRs characterized by low/moderate mutation rate and middle/high polymorphic was amplified simultaneously in a multiplex PCR system using the six color labeling fluorescence. PCR product was analyzed in a ABI 3500XL Genetic Analyzer. The accuracy, specifity, sensitivity and stability of the system and its validation on the mixtures were evaluated. Results The validation studies demonstrated that the system is a stable, accurate, and sensitive multiplex PCR system. The sensitivity was 0.0625ng DNA. Y-STR could be detection in a male/female DNA mixture ratio of 1:4. Conclusion The primary study demonstrates that this multiplex PCR system is effective and reliable for forensic routine DNA analysis. It will be very helpful for constructing Chinese forensic Y-STR database and population genetic research.
7.Genetic Polymorphisms and Mutations of 30 Y-STR Loci in Chinese Han Population.
Wei Wei WU ; Yan Jia SU ; Xing Lin MEI ; De Jian LÜ ; Xiang ZHOU ; Hong Lei HAO ; Wen Yan REN ; Bing LIU
Journal of Forensic Medicine 2018;34(4):411-416
OBJECTIVES:
To investigate the genetic polymorphisms and mutations of 30 Y-STR loci in Chinese Han males and to evaluate its forensic application.
METHODS:
The DNA extracted from blood samples of 1 005 unrelated males and 1 008 father-son pairs (1 949 individuals in all) in Chinese Han population were typed using developed 30 Y-STR loci identification system. The parameters of population genetics and the mutation rates of each locus were analysed statistically.
RESULTS:
A total of 983 haplotypes were found in 1 005 unrelated males from Chinese Han population, of which 963 were unique. The overall haplotype diversity (HD) and discrimination capacity (DC) were 0.999 955 and 0.978 109, respectively. Totally 340 alleles were detected on 30 Y-STR loci, the value of gene diversity (GD) ranged from 0.410 3 to 0.952 3. The GD values of 24 out of the 30 loci were over 0.6. There were 30 269 allele transfers in 1 008 father-son pairs, one mutation in 68 father-son pairs, and the mutation of three father-son pairs occurred at two loci. On 26 Y-STR loci, 74 mutations were detected in 71 father-son pairs. The average mutation rates were 2.4×10⁻³ (95% CI: 1.9×10⁻³-3.1×10⁻³). Seventy-three mutation events were one-step mutation (98.6%), 1 mutation event was two-step mutation (1.4%).
CONCLUSIONS
The multiplex PCR system with 30 Y-STR loci has high genetic polymorphism and low mutation rates in Chinese Han males. Therefore, the system shows important values in Y-STR database construction and population genetic research.
Alleles
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Asian People/genetics*
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China
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Chromosomes, Human, Y/genetics*
;
Gene Frequency
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Genetic Variation
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Genetics, Population
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Haplotypes
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Humans
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Male
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Multiplex Polymerase Chain Reaction
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Mutation/genetics*
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Mutation Rate
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Polymorphism, Genetic
8.Improving qualified rate of cleaning of loaner orthopedic surgery instruments by application of quality control circle
Li-Hua ZHONG ; Hong-Mei WANG ; Su-Tao REN ; Ling-Long ZHAO ; Ping XIANG ; Xiao-Yan LIAO
Chinese Journal of Infection Control 2018;17(3):267-269
Objective To improve the qualified rate of cleaning of loaner orthopedic surgery instruments by application of quality control circle(QCC).Methods QCC activity was carried out in a hospital from May to October 2016, on-site assessment of cleaning quality was performed by two circle members, causes of unqualified cleaning result of loaner orthopedic surgery instruments were recorded, the qualified result of loaner orthopedic surgery instruments before QCC activity(May-June 2016)and after QCC activity(September-October 2016)was compared. Results Before QCC activity, there were 1 667 packages of loaner instruments, 1 415 were qualified for cleaning, qualified rate was 84.88%;after activity, there were 1 673 packages of loaner instruments, 1 655 were qualified for cleaning, qualified rate was 98.92%, difference was statistically significant between two groups(P<0.01), qualified rate increased to 14.04%, target achievement rate was 116%.Conclusion Application of the scientific tool of QCC can improve the qualified rate of cleaning of loaner orthopedic surgery instruments.
9.Depression and anxiety caused by pegylated interferon treatment in patients with chronic hepatitis B and the therapeutic effects of escitalopram and alprazolam.
Cheng-Guang HU ; Guo-Sheng YUAN ; Hua-Ping HUANG ; Jun-Wei LIU ; Yu-Chen ZHOU ; Yan-Yu REN ; Yuan LI ; Wen-Juan TAN ; Mei-Lei SU ; Yuan-Ping ZHOU
Journal of Southern Medical University 2017;37(9):1201-1205
OBJECTIVETo evaluate the incidence of depression and anxiety caused by pegylated interferon α (PegIFN-α) treatment for chronic hepatitis B (CHB) and assess the efficacy of intervention with escitalopram and alprazolam.
METHODSA total of 165 CHB patients receiving PegIFN-α-based treatment for 12 weeks were assessed for moderate to severe depression and anxiety using Patient Health Questionnaire (PHQ-9) and 7-item Generalized Anxiety Disorder Scale (GAD-7)]. The patients identified to have moderate to severe depression and anxiety treated with escitalopram or alprazolam and the psychological condition of the patients was assessed at the 2nd, 4th and 8th weeks of the treatments.
RESULTSIn the 165 patients receiving PegIFN-α treatment, 51 patients developed moderate to severe psychiatric symptoms, incuding 37 (22.4%) with depression, 31 (18.8%) with anxiety, and 17 (10.3%) with both. The symptoms of depression and anxiety was both significantly improved by intervention with escitalopram (P=0.000); alprazolam was effective for anxiety (P=0.001) but did not produce obvious effects on depression (P=0.904). Nevertheless, alprazolam had a much better therapeutic effect than escitalopram on anxiety in these patients (t=-3.198, P=0.010).
CONCLUSIONPsychological symptoms are common in CHB patients receiving PegIFN-α treatment. The symptoms of depression and anxiety can be ameliorated by intervention with escitalopram and alprazolam, respectively.
10.Bioequivalence of candesartan cilexeticcapsule in Chinese healthy subjects
Su-Mei XU ; Ren GUO ; Dan LI ; Xiao-Min LI ; Dai LI
The Chinese Journal of Clinical Pharmacology 2017;33(6):509-512
Objective Toinvestigate the bioequivalence of domestic can desartan cilexetil capsules and imported candesartan cilexetil tablets in Chinese healthy subjects.Methods This is open,random and two way crossover clinical trial involved 24 healthy male subjects.A single oral dose 8 mg of domestic candesartan cilexetil capsules (test preparation) and imported candesartan cilexetil tablets (control preparation) was administrated under the condition of fasting.The plasma concentrations of candesartan were determined by LC-MS/MS.The pharmacokinetics parameters were calculated and the bioequivalence of two formulations were evaluated by WinNonlin program.Results The main pharmacokinetic parameters of the test and control preparation were as follows:t1/2 (9.30±1.70),(9.80 ± 1.90) h;tmax(4.00 ±0.80),(4.20 ± 1.00) h;Cmax (76.98 ± 22.22),(87.35 ±34.61) μg· L-1;AUC0-48h (826.60 ± 204.10),(928.00 ± 269.30) μg · h · L-1;AUC0-∞ (857.10 ±201.30),(956.10 ± 270.60) μg · h · L-1.The relative bioavailability of the test preparation (candesartan cilexetil capsules) was (114.40 ±27.30) %.And 90% confidence limit of test preparation of the logarithmic transformed parameters AUC0-48h,AUC0-∞,Cmax were in 101.37%-121.80%,101.08%-120.15%,98.59%-119.54% compared with reference preparation,respectively.No significant difference was found by nonparametric test of tmax.Conclusion The developed and validated method is rapid,sensitive,selective and reliable for the determination of candesartan in human plasma.The domestic candesartan cilexetil capsules are bioequivalence to the imported candesartan cilexetil tablets.

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