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.

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 investigate the material basis of homologous and heterogeneous effect of Aurantii Fructus Immaturus（AFI） and Aurantii Fructus（AF） based on the total statistical moment analysis and molecular connectivity index（MCI）. MethodRelevant literature at home and abroad and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） were consulted to establish the chemical composition database of AFI and AF， and set up their fingerprints by ultra-high performance liquid chromatography（UPLC）， and the total statistical moments and similarity parameters of the fingerprint were calculated. According to MCI， all components of AFI and AF were divided into different component groups， the average values of 0-8^th order（⁰χ-⁸χ） MCI of the common component groups of AFI and AF were calculated. ResultThe values of total zero-order moment（AUC_T） of AFI and AF were （10.57±2.45）×10⁶， （5.09±0.89）×10⁶ μV·s， the values of total first-order moment（MCRT_T） were （11.57±1.58）， （12.10±1.29） min， the values of total second-order moments（VCRT_T） were（24.49±2.30）， （26.49±2.54） min²， respectively. It showed that qualitative and quantitative parameters of AFI and AF were significantly different. The components with high similarity such as neohesperidin， hesperidin and narirutin were screened as the common potential pharmacodynamic components of AFI and AF. The non-common components of AFI， such as alysifolinone and imperatorin， and the non-common components of AF， such as neoeriocitrin and isosakuranin， with high similarity were screened out as potential heterogeneous components of AFI and AF. The composition groups of AFI and AF were classified into six categories， and the similarities between the composition groups of AFI and AF and the total constituents were 0.872-0.979 and 0.918-0.997， the average values of ⁰χ-⁸χ MCI of alkaloids in AFI and AF were 3.65 and 3.14， the average values of ⁰χ-⁸χ MCI of flavonoids were 8.47 and 8.47， the average values of ⁰χ-⁸χ MCI of volatile oils were 2.71 and 3.48， respectively. It showed that there were some differences in MCI of chemical constituents（groups） between AFI and AF. ConclusionThe chemical constituents（groups） of AFI and AF not only differ in content and species， but also in structural characteristics and structure-activity relationship， which can provide a basis for further explaining the scientific connotation of homologous and heterogeneous effect of AFI and AF.

Objective:To investigate the correlation between the promoter methylation level of Dickkopf-related protein 1 (DKK1) gene and diabetic microangiopaopathy complicated with osteoporosis.Methods:Patients with type 2 diabetes mellitus (T2DM) microangiopathopathy who were admitted to our hospital from Jan. 2019 to Dec. 2022 were collected as research objects, and divided into observation group (44 cases) and control group (58 cases) according to whether they were complicated with osteoporosis. Bone mineral density (BMD) of lumbar spine (L1-4) was measured, and bone metabolism indexes, including serum calcium, serum phosphorus, 25-hydroxy vitamin D3[25-hydroxy vitamin D3, 25- (OH) D3], PTH, C-terminal telopeptide of typeI collagen (CTX), procollagen of aminoterminal propeptide (PINP) and tartrate resistant acid phosphatase (TRACP) levels were detected; The promoter methylation level of DKK1 gene was determined.Results:The methylation level of DKK1 gene promoter in the observation group was 5.17%±0.73%, which was significantly higher than that in the control group (3.81%±0.61%), with statistical significance ( t=5.22, P<0.001). The 25- (OH) D3 level, PTH and lumbar bone density in the observation group were significantly lower than those in the control group, while the CTX and TRACP levels were significantly higher than those in the control group ( t was 5.58, 4.35, 4.12, 4.05 and 4.17, respectively, P<0.001). In all patients, the promoter methylation level of DKK1 gene was significantly positively correlated with CTX and TRACP ( r was 0.41 and 0.39, P was 0.006 and 0.027, respectively), and significantly negatively correlated with PTH and lumbar bone density ( r was -0.38 and -0.43, respectively). P=0.015 and 0.003, respectively). ROC curve analysis showed that the area under the curve of DKK1 methylation level to distinguish type 2 diabetes microangionopathy with and without osteoporosis was 0.841 (0.762-0.921), and the sensitivity and specificity were 86.4% and 72.4%, respectively. Conclusion:The methylation level of DKK1 gene promoter is associated with osteoporosis and bone metabolism in T2DM patients with microangiopathia.

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".

Objective:To retrospectively analyze the dual plasma molecular adsorption system (DPMAS) treatment technology and the laboratory data before and after treatment in patients with liver failure and refractory hyperbilirubinemia, so as to provide a clinical basis for the prediction and prevention of common related complications.Method:A retrospective study was conducted on 161 cases with liver failure and 68 cases with refractory hyperbilirubinemia who underwent DPMAS treatment in our department from October 2022 to July 2024. The general clinical data characteristics, DPMAS treatment status, DPMAS-related complications, and changes in important laboratory indicators before and after the initial DPMAS treatment in both patient groups were analyzed.Results:Among the 229 enrolled cases, 82.53% were male, and the median age was 50 years. The cause of liver failure was hepatitis B virus infection in 84.47%, while hepatitis B accounted for only 51.47% in the other group. There were significant differences in platelets, creatinine, coagulation function, and inflammatory factor-related indicators between the two groups at baseline. The total number of DPMAS treatments given was 471 times. The proportion of albumin used in the initial stage of treatment was significantly higher in patients with refractory hyperbilirubinemia than that in the liver failure group, while the proportion of plasma used in the liver failure group was significantly higher ( P<0.001). The most commonly used anticoagulation regimen was unfractionated heparin. A combined anticoagulation therapy regimen was used in 9.3% of the refractory hyperbilirubinemia group. The internal jugular vein was selected in nearly half of the treated cases. A peripheral vascular access pathway was the treatment option in 31.2%. The proportion of centrifugal separation was significantly higher than that of membrane separation (76.22% vs. 23.78%). The incidence rate of DPMAS-related complications was 16%. The most common complication was bleeding, including bleeding at the puncture site (accounting for 32% of the total complications) and bleeding at non-puncture sites (12%), followed by hypotension (22%), allergic reactions (13%) and infections (11%), respectively. The indexes of hemoglobin, platelets, total bilirubin, and C-reactive protein were significantly decreased within 24-48 hours after DPMAS treatment in both groups of patients. The prothrombin time and international normalized ratio were significantly increased in the liver failure group, while fibrinogen was significantly reduced. Conclusion:DPMAS clinical application is generally safe in patients with liver disease. The most common complications are bleeding, hypotension, allergic reactions, and infections, which need to be paid special attention and timely intervention to ensure the safety profile of treatment.

Objective:To retrospectively analyze the dual plasma molecular adsorption system (DPMAS) treatment technology and the laboratory data before and after treatment in patients with liver failure and refractory hyperbilirubinemia, so as to provide a clinical basis for the prediction and prevention of common related complications.Method:A retrospective study was conducted on 161 cases with liver failure and 68 cases with refractory hyperbilirubinemia who underwent DPMAS treatment in our department from October 2022 to July 2024. The general clinical data characteristics, DPMAS treatment status, DPMAS-related complications, and changes in important laboratory indicators before and after the initial DPMAS treatment in both patient groups were analyzed.Results:Among the 229 enrolled cases, 82.53% were male, and the median age was 50 years. The cause of liver failure was hepatitis B virus infection in 84.47%, while hepatitis B accounted for only 51.47% in the other group. There were significant differences in platelets, creatinine, coagulation function, and inflammatory factor-related indicators between the two groups at baseline. The total number of DPMAS treatments given was 471 times. The proportion of albumin used in the initial stage of treatment was significantly higher in patients with refractory hyperbilirubinemia than that in the liver failure group, while the proportion of plasma used in the liver failure group was significantly higher ( P<0.001). The most commonly used anticoagulation regimen was unfractionated heparin. A combined anticoagulation therapy regimen was used in 9.3% of the refractory hyperbilirubinemia group. The internal jugular vein was selected in nearly half of the treated cases. A peripheral vascular access pathway was the treatment option in 31.2%. The proportion of centrifugal separation was significantly higher than that of membrane separation (76.22% vs. 23.78%). The incidence rate of DPMAS-related complications was 16%. The most common complication was bleeding, including bleeding at the puncture site (accounting for 32% of the total complications) and bleeding at non-puncture sites (12%), followed by hypotension (22%), allergic reactions (13%) and infections (11%), respectively. The indexes of hemoglobin, platelets, total bilirubin, and C-reactive protein were significantly decreased within 24-48 hours after DPMAS treatment in both groups of patients. The prothrombin time and international normalized ratio were significantly increased in the liver failure group, while fibrinogen was significantly reduced. Conclusion:DPMAS clinical application is generally safe in patients with liver disease. The most common complications are bleeding, hypotension, allergic reactions, and infections, which need to be paid special attention and timely intervention to ensure the safety profile of treatment.