Objective To evaluate the quality of Shuanghuanglian Oral Liquid after mutual substitution of honeysuckle and wild honeysuckle using total quantum statistical moment(TQSM)and molecular connectivity index(MCI).Methods UPLC fingerprint of Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian oral liquid(wild honeysuckle)were established,the TQSM parameters and similarity of the fingerprint were calculated;by reviewing relevant literature,as well as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),chemical composition databases for Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian Oral Liquid(wild honeysuckle)was established,all components were divided into different component groups,and MCI and its similarity were calculated.Results The number of chromatographic peaks and total zero order moment(AUCT)of 15 batches of Shuanghuanglian Oral Liquid(honeysuckle)were higher than those of Shuanghuanglian Oral Liquid(wild honeysuckle),but there was no significant difference in total first order moment(MRTT)and total second order moment(VRTT);the total quantum statistical moment similarity(TQSMS)between 15 batches of Shuanghuanglian Oral Liquid(honeysuckle)was 1.000 0-0.824 6,the TQSMS between 15 batches of Shuanghuanglian Oral Liquid(wild honeysuckle)was 1.000 0-0.659 0,and the TQSMS between 15 batches of Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian Oral Liquid(wild honeysuckle)was 1.000 0-0.619 8.The MCI similarity of various components between Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian Oral Liquid(wild honeysuckle)was 1.000 0-0.984 9,with an overall MCI similarity of 0.995 8.Conclusion There is no significant difference in the various components and overall"imprinting template"between Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian Oral Liquid(wild honeysuckle).It is speculated that the substitution of honeysuckle and wild honeysuckle will not affect the pharmacological properties of Shuanghuanglian Oral Liquid,but there may be differences in the intensity of pharmacological effects,with Shuanghuanglian Oral Liquid(honeysuckle)being the most effective.

Objective To establish the fingerprints of Buyang Huanwu Decoction;To find the quality markers of Buyang Huanwu Decoction by integrating the total statistical moment method,factor analysis and chemical pattern recognition;To provide a reference for its quality control and evaluation methods.Methods Under the conditions of an ACQUITY UPLC HSS T3 column(2.1 mm×100 mm,1.8 μm),the fingerprint chromatogram was developed.The fingerprints of 15 batches of Buyang Huanwu Decoction were established under the conditions of acetonitrile-0.4%phosphoric acid aqueous solution as the mobile phase;the flow rate was 0.3 mL/min;column temperature was 40℃;detection wavelength was 235 nm.Information entropy,information quantity,total statistical moment and similarity parameters were calculated.The quality stability of different batches of Buyang Huanwu Decoction was evaluated from a macroscopic perspective;the samples were comprehensively ranked by combining factor analysis,and further screened for the components of quality difference by using hierarchical cluster analysis(HCA),principal component analysis(PCA)and partial least squares-discriminant analysis(PLS-DA).Results Fingerprint patterns for 15 Buyang Huanwu Decoction batches were established.The information quantity,total zero-order moment and number of peaks varied greatly among the samples of each batch(RSD values of 32.788%,24.976%and 22.882%),whereas the information entropy,total first-order moment and second-order moment did not vary much(RSD values of 20.697%,18.544%and 9.413%),which indicated that the chemical constituents of each batch content was significantly different,and the composition ratio of components did not differ much.The overall statistical moments exhibited a similarity exceeding 0.727,in which the similarity of the two batches of samples,S2 and S7,was lower;the results of the composite scores from the factor analysis method showed that the top 5 samples of each batch of the quality ranking were S2>S7>S1>S15>S10;HCA and PCA could classify the 15 batches of samples into 2 categories;PLS-DA showed that paeoniflorin,ferulic acid and hydroxy saffron yellow pigment A were the three constituents that contributed more to the batch variation of Buyang Huanwu Decoction.Conclusion The multidimensional quality evaluation method integrated in this study is accurate,efficient and comprehensive,which can provide an objective basis for the overall quality control of Buyang Huanwu Decoction.

Objective To evaluate the quality of Shuanghuanglian Oral Liquid after mutual substitution of honeysuckle and wild honeysuckle using total quantum statistical moment(TQSM)and molecular connectivity index(MCI).Methods UPLC fingerprint of Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian oral liquid(wild honeysuckle)were established,the TQSM parameters and similarity of the fingerprint were calculated;by reviewing relevant literature,as well as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),chemical composition databases for Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian Oral Liquid(wild honeysuckle)was established,all components were divided into different component groups,and MCI and its similarity were calculated.Results The number of chromatographic peaks and total zero order moment(AUCT)of 15 batches of Shuanghuanglian Oral Liquid(honeysuckle)were higher than those of Shuanghuanglian Oral Liquid(wild honeysuckle),but there was no significant difference in total first order moment(MRTT)and total second order moment(VRTT);the total quantum statistical moment similarity(TQSMS)between 15 batches of Shuanghuanglian Oral Liquid(honeysuckle)was 1.000 0-0.824 6,the TQSMS between 15 batches of Shuanghuanglian Oral Liquid(wild honeysuckle)was 1.000 0-0.659 0,and the TQSMS between 15 batches of Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian Oral Liquid(wild honeysuckle)was 1.000 0-0.619 8.The MCI similarity of various components between Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian Oral Liquid(wild honeysuckle)was 1.000 0-0.984 9,with an overall MCI similarity of 0.995 8.Conclusion There is no significant difference in the various components and overall"imprinting template"between Shuanghuanglian Oral Liquid(honeysuckle)and Shuanghuanglian Oral Liquid(wild honeysuckle).It is speculated that the substitution of honeysuckle and wild honeysuckle will not affect the pharmacological properties of Shuanghuanglian Oral Liquid,but there may be differences in the intensity of pharmacological effects,with Shuanghuanglian Oral Liquid(honeysuckle)being the most effective.

Objective To establish the fingerprints of Buyang Huanwu Decoction;To find the quality markers of Buyang Huanwu Decoction by integrating the total statistical moment method,factor analysis and chemical pattern recognition;To provide a reference for its quality control and evaluation methods.Methods Under the conditions of an ACQUITY UPLC HSS T3 column(2.1 mm×100 mm,1.8 μm),the fingerprint chromatogram was developed.The fingerprints of 15 batches of Buyang Huanwu Decoction were established under the conditions of acetonitrile-0.4%phosphoric acid aqueous solution as the mobile phase;the flow rate was 0.3 mL/min;column temperature was 40℃;detection wavelength was 235 nm.Information entropy,information quantity,total statistical moment and similarity parameters were calculated.The quality stability of different batches of Buyang Huanwu Decoction was evaluated from a macroscopic perspective;the samples were comprehensively ranked by combining factor analysis,and further screened for the components of quality difference by using hierarchical cluster analysis(HCA),principal component analysis(PCA)and partial least squares-discriminant analysis(PLS-DA).Results Fingerprint patterns for 15 Buyang Huanwu Decoction batches were established.The information quantity,total zero-order moment and number of peaks varied greatly among the samples of each batch(RSD values of 32.788%,24.976%and 22.882%),whereas the information entropy,total first-order moment and second-order moment did not vary much(RSD values of 20.697%,18.544%and 9.413%),which indicated that the chemical constituents of each batch content was significantly different,and the composition ratio of components did not differ much.The overall statistical moments exhibited a similarity exceeding 0.727,in which the similarity of the two batches of samples,S2 and S7,was lower;the results of the composite scores from the factor analysis method showed that the top 5 samples of each batch of the quality ranking were S2>S7>S1>S15>S10;HCA and PCA could classify the 15 batches of samples into 2 categories;PLS-DA showed that paeoniflorin,ferulic acid and hydroxy saffron yellow pigment A were the three constituents that contributed more to the batch variation of Buyang Huanwu Decoction.Conclusion The multidimensional quality evaluation method integrated in this study is accurate,efficient and comprehensive,which can provide an objective basis for the overall quality control of Buyang Huanwu Decoction.

Objective The characteristics of supramolecular"imprinting template"of volatile oil of Curcuma kwangsiensis and Curcuma phaeocaulis were analyzed and studied based on the supramolecular"qixi"theory of Chinese materia medica combined with chemometrics.Methods The volatile oil of C.kwangsiensis and C.phaeocaulis were extracted by steam distillation,and the fingerprint and composition information of each batch were obtained by GC-MS.Total statistical moment method was used to compare the imprinting characteristics of the"imprinting template"of C.kwangsiensis and C.phaeocaulis.The core index(CI)of each batch of essential oil of C.kwangsiensis and C.phaeocaulis was calculated,and the topological characteristics of types of"imprinting template"of C.kwangsiensis and C.phaeocaulis were compared by chemometrics.Results There was no significant difference in the extraction rate of volatile oil between C.kwangsiensis and C.phaeocaulis.The average values of total zero order moment(AUCT)were(1.907±0.177)×108,(1.979±0.413)×108 μV·s,respectively,showing that there was no significant difference in the total content of volatile oil between the two groups.The mean values of the total first order moment(MCRTT)were(30.969±0.962)and(33.198±0.409)min.The average value of total second order moment(VCRTT)was(56.176±11.368)and(43.891±4.113)min2,respectively,indicating that there were significant differences in the content ratio and species of volatile oils between the two groups.The similarity of total statistical moments of C.kwangsiensis and C.phaeocaulis was mostly lower than the defined value,indicating that the chemical composition and composition ratio of the volatile oil were different.Principal component analysis and orthogonal partial least squares discriminant analysis could obviously divide C.kwangsiensis and C.phaeocaulis into two categories.Through the analysis of P value and VIP value,the CI values of Xvp 4th order,Xvpc 5th order,Xvpc 6th order,Xvpc 7th order,Xvc 3rd order,Xvpc 4th order were the main difference values of C.kwangsiensis and C.phaeocaulis.Conclusion Through the characterization of"imprinting property"and"topological characteristics"of the supramolecular"imprinting template"and combining with chemometric analysis,it is possible to successfully distinguish C.kwangsiensis and C.phaeocaulis,and find the different CI values between two"imprinting templates".

ObjectiveBased on the network pharmacology system and quantitative spectroscopy of traditional Chinese medicine（TCM） compounds， a topological network analysis method with equilibrium constant as the core was established to further explore the interaction between allergenic components and their network targets in Shuanghuanglian injection（SHLI）， in order to provide new ideas and experimental basis for identifying and screening potential allergens of SHLI. MethodAfter one week of adaptive feeding， 72 SPF-grade SD male rats were randomly divided into blank group， SHLI standard group， Lonicerae Japonicae Flos（LJF） group， Scutellariae Radix（SR） group， Forsythiae Fructus（FF） group， and 7 groups of SHLI matching groups（groups 1-7）， with 6 rats in each group. Rats in each group were administered the drug intravenously and blood samples were taken after steady state， high performance liquid chromatography（HPLC） characterization profiles of the testing drugs and plasma components in each group were established， and the peak area changes of the drugs and plasma components in each group were calculated after the component groups were classified. Enzyme-linked immunosorbent assay（ELISA） was used to determine the changes of immunoglobulin E（IgE）， histamine（HIS）， tryptase（TPS）， total complement（CH50） and terminal complement complex（C5b-9） in animal blood samples. MATLAB R2020b v9.9.0 software was used to calculate the network balance constants of the component groups with the targets， and the eigenvalues of the matrices composed of network equilibrium constants were calculated and ranked according to their values. ResultELISA results showed that， compared with the blank group， groups 1-3 could significantly increase the IgE level， groups 1-2， groups 4-6 and SHLI standard group could significantly increase the HIS level， group 4 could significantly increase the CH50 level， groups 1， 3-4， LJF group and FF group could significantly increase the TPS level， SR group could significantly increase the C5b-9 level， and the differences were all statistically significant（P<0.05）. According to the retention time of chromatographic peaks， it was classified into 6 component groups from C1 to C6 by HPLC. The order of the network balance constants of each component group was C6>C4>C1>C5>C3>C2， indicating that C6 had the greatest effect on the allergic reaction， and was most likely to be the allergen. The sequence of eigenvalues was C2>C5b-9>C3>C1>CH50>C6>C5>IgE>TPS>C4>HIS， indicating that component group C2 had the greatest contribution to the whole network. ConclusionBased on the correlation analysis of SHLI component group and allergy-like target network， this study clarified that component group C6 may be a potential allergen in SHLI， and the component group C2 may be a key node in the mechanism of drug action， which can provide new strategies and methods for the screening of allergens in TCM injections.

ObjectiveTo establish a theoretical system of pharmacokinetic and spectrokinetic dose-time characterization of traditional Chinese medicine（TCM）. By analyzing the pharmacokinetic and spectrokinetic behaviors of Lonicerae Flos， Houttuyniae Herba injection， Lonicerae Japonicae Flosand Buyang Huanwutang， this paper compared the similarities and differences of the three methods for characterizing the dose-time relationship， namely half-life， statistical moment and statistics， in order to find the most suitable method for characterizing the relationship. MethodTen mice were randomly selected from 100 Kunming mice as the blank group， and the remaining mice were coated with xylene in the auricle to establish the acute inflammation model of ear swelling. After successful modeling， the mice were gavaged with aqueous extract of Lonicerae Flos（30 g∙kg^-1）， and the blank group was gavaged with an equal volume of normal saline. The plasma of mice was collected at different time points to determine the content changes of components. At the same time， the pharmacokinetic results of Houttuyniae Herba injection， Lonicerae Japonicae Flos and Buyang Huanwutang were included， and the pharmacokinetic and spectrokinetic parameters were calculated. Then the difference in the time of calculating 95% total component content of metabolism by half-life method， statistical moment method and statistical method was compared. ResultOn the basis of the half-life method， the mathematical expressions of statistical moment method and statistical method suitable for the characterization of dose-time relationship of multi-component system of TCM were established. The results showed that the pharmacokinetic parameters of the individual components in Lonicerae Flos varied， with cryptochlorogenic acid and rutin showing a two-compartment model and the other components showing a one-compartment model. After calculation of spectrokinetic similarity， the metabolic patterns among the components contained in Houttuyniae Herba injection， Lonicerae Japonicae Flos， Lonicerae Flos and Buyang Huanwutang were different and varied greatly in vivo. The time to metabolize 95% of the total components of the four research subjects in vivo was calculated by the half-life method， statistical moment method and statistical method， and it was found that the difference between statistical moment method and half-life method was large， and the difference between statistical moment method and statistical method was small. ConclusionStatistical method not only reflects the characteristics of statistical moment method， characterizes the dispersion degree of each component， but also can be associated with fingerprint to form spectrokinetics， characterizing the dose-time relationship of 95% of drug components， which is a more desirable method to characterize the dose-time relationship of the component groups in TCM.

Objective To investigate the influence of epidural analgesia on labor duration under the new partogram recommendations using quantile regression.Methods In this study,we recruited 300 nulliparous women at full term who were hospitalized in Department of Obstetrics and Gynecology,Tongji Medical College,Huazhong University of Science and Technology from May to September,2018.The participants who were willing to receive epidural analgesia during labor were assigned to the epidural group (n=150),and those who were not to the control group (n=150).Labor duration and delivery outcomes were analyzed by Student's t test,Mann-Whitney U test,Chi-square test and Fisher's exact test.Quantile regression models were also used to investigate the effect of epidural analgesia on labor duration.Results The median durations of first-and second-stage labor in the epidural group were 600(400-840) and 66(45-98) min,respectively,which were significantly longer than those of the control group [420(320-610) and 52(33-87) min] (Z=-4.273,P＜0.001;Z=-3.210,P=0.001).Quantile regression analysis showed that,for the first stage of labor,epidural analgesia was associated with labor prolongation,and had significant effects on all the percentiles (all P＜0.05).The regression coefficients increased (95.630-285.000) correspondingly as the percentiles of the labor duration (from 10th to 90th percentiles) increased.For the second stage of labor,epidural analgesia showed a significant impact on prolongation only between the 25th and 75th percentiles (coefficients:10.000～18.143;all P＜0.05).Although the epidural group had a significant higher episiotomy rate [46.8％(65/139) vs 33.3％(48/144),x2=5.318,P=0.021],more times of urine catheterization during labor [1(0-1) vs 0(0-1),Z=-0.974,P=0.001]and higher rate of oxytocin administration during labor [48.7％(73/150) vs 30.0％(45/150),x2=10.952,P=0.001],when compared with the control group,there was no significant difference in cesarean section rate,assisted vaginal delivery rate and neonatal outcomes between the two groups (all P＞0.05).Conclusions Epidural analgesia may associated with the prolongation of the first and second stage of labor,especially with the first stage of labor,but has no adverse effects on maternal and neonatal outcomes.

Objective To investigate the correlation between 24 h urinary protein quantitation and pregnancy outcome in patients with pre-eclampsia.Methods A total of 332 pre-eclampsia patients were selected in Tongji Hospital from January 2014 to December 2016.The patients were divided into microalbuminuria group(24 h urinary protein quantification ＜ 0.3 g,n =46),mild proteinuria group (0.3 g ≤ 24 h urinary protein quantification ＜ 2.0 g,n =98),moderate proteinuria group (2.0 g ≤ 24 h urinary protein quantification ＜ 5.0 g,n =71) and severe proteinuria group(24 h urinary protein quantification ≥ 5.0 g,n =117) according to the results of 24 h urinary protein quantification.The pregnancy outcomes were compared between the four groups.Results The 24 h urinary protein quantification and the serum creatinine,urea nitrogen,uric acid levels in the mild proteinuria group,moderate proteinuria group and severe proteinuria group were significantly higher than those in the microalbuminuria group (P ＜ 0.05);and gestational week was significantly shorter than that in the microalbuminuria group (P ＜ 0.05).The 24 h urinary protein quantification and serum urea nitrogen,uric acid levels in the moderate proteinuria group were significantly higher than those in the mild proteinuria group (P ＜ 0.05);and gestational week was significantly shorter than that in the mild proteinuria group (P ＜ 0.05);but there was no significant difference in serum creatinine level between the two groups (P ＞ 0.05).The 24 h urinary protein quantification,serum creatinine,urea nitrogen and uric acid levels in the severe proteinuria group were significantly higher than those in the mild proteinuria group (P ＜ 0.05);and the gestational week was significantly lower than that in the mild albuminuria group (P ＜ 0.05).The 24 h urinary protein quantification in the severe proteinuria group was significantly higher than that in the moderate proteinuria group (P ＜ 0.05),but there was no significant difference in the gestational week and serum creatinine,urea nitrogen,uric acid levels between the two groups (P ＞0.05).There was no significant difference in the rates of cesarean section and spontaneous labor between the four groups (P ＞0.05).The rate of induced labor in the moderate proteinuria group and the severe proteinuria group was significantly higher than that in the mild albuminuria group and the microalbuminuria group (P ＜ 0.05).There was no significant difference in the rate of induced labor between the mild proteinuria group and the microalbuminuria group (P ＞ 0.05).There was no significant difference in the rate of induced labor between the severe proteinuria group and the moderate proteinuria group (P ＞ 0.05).The incidence of complications in microalbuminuria group,mild proteinuria group,moderate proteinuria group and severe proteinuria group was 30.43％ (14/46),47.96％ (47/98),74.65％ (53/71) and 74.36％ (87/117) respectively;the incidence of complications in the moderate proteinuria group and the severe proteinuria group was significantly higher than that in the microalbuminuria group and the mild albuminuria group (P ＜ 0.05),but there was no significant difference in the incidence of complications between microalbuminuria group and mild albuminuria group (P ＞ 0.05),there was no significant difference in the incidence of complications between the moderate proteinuria group and the severe proteinuria group (P ＞0.05).The incidences of premature birth and neonatal asphyxia in the mild proteinuria group were significantly higher than that in the microalbuminuria group (P ＜ 0.05),and the body mass of the neonates was significantly lower than that in the microalbuminuria group (P ＜0.05),but there was no significant difference in the perinatal mortality rate and the incidences of fetal growth restriction(FGR) and poor neonatal resuscitation between the two groups (P ＞ 0.05).The incidences of FGR,premature birth,neonatal asphyxia,poor neonatal resuscitation and the perinatal mortality in the moderate proteinuria group and severe proteinuria group were significantly higher than those in the microalbuminuria group (P ＜ 0.05);and neonatal body mass was significantly lower than that in the mieroalbuminuria group (P ＜ 0.05).The incidences of FGR,premature birth and poor neonatal resuscitation and perinatal mortality in the moderate proteinuria group were significantly higher than those in the mild proteinuria group (P ＜ 0.05);and the neonatal body mass was significantly lower than that in the mild proteinuria group (P ＜ 0.05);but there was no significant difference in the neonatal asphyxia incidence between the two groups (P ＞ 0.05).The incidences of FGR,premature birth,neonatal asphyxia,poor neonatal resuscitation and perinatal mortality in the severe proteinuria group were significantly higher than those in the mild proteinuria group (P ＜ 0.05);and the body mass of the newborns was significantly lower than that in the mild albuminuria group (P ＜ 0.05).The incidence of neonatal asphyxia in the severe proteinuria group was significantly higher than that in the moderate proteinuria group (P ＜ 0.05),but there was no significant difference in the incidences of FGR,premature birth,poor neonatal resuscitation,perinatal mortality and neonatal body mass between the two groups (P ＞ 0.05).Conclusions The of 24 h urinary protein quantitation is closely related to the pregnancy outcome in patients with pre-eclampsia,the 24 h urinary protein quantification should be regularly detected in the patients with pre-eclampsia.When the urinary protein quantitation is more than 2.0 g,the incidences of maternal complications and poor prognosis of the perinatal infants is significantly higher,but the boundary value of the 24 h urinary protein quantitation for the diagnosis of severe pre-eclampsia still needs further large sample study.

This study investigated the effect of epigenetic modification of maspin on extravillous trophoblastic function. The mRNA expression of maspin in placentae from normotensive and preeclamptic pregnant women was detected by RT-PCR. TEV-1 cells, a human first-trimester extravillous trophoblast cell line, were cultured and treated with CoCl(2) (300 μmol/L) to induce chemical hypoxia and with 5-aza (500 nmol/L) to induce demethylation. The mRNA expression of maspin in TEV-1 cells subjected to different treatments was determined by RT-PCR, and the proliferative and migratory abilities of TEV-1 cells were assessed by cell counting kit-8 (CCK-8) and Transwell assays. Our results showed that the maspin mRNA expression level in placentae from preeclamptic women was much higher than that from normotensive women. CoCl(2) or 5-aza could up-regulate the mRNA expression of maspin and significantly suppress the proliferation and migration of TEV-1 cells. It was concluded that the epigenetic modification in promoter region of maspin contributes to incomplete trophoblast invasion, which offers a novel approach for predicting and treating placental dysfunction.
Adult ; Chorionic Villi ; physiology ; Epigenesis, Genetic ; genetics ; Female ; Humans ; Pregnancy ; Serpins ; genetics ; Trophoblasts ; physiology