ObjectiveTo establish a method for the identification of Haliotidis Concha and its counterfeits， and to improve its quality evaluation method. MethodsA total of 17 batches of Haliotis discus hannai， 4 batches of H. ruber， 3 batches of H. laevigata， 3 batches of H. ovina， 3 batches of H. diversicolor， 3 batches of H. asinina， 3 batches of H. iris were collected. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive-Orbitrap-MS/MS） was used to analyze the hydrolysates of different original Haliotidis Concha and its counterfeits， and the potential characteristic ions of each species were screened by Venn diagram. UPLC-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS） was used to validate the characteristic ions， and the specific detection method of the characteristic ions was established. ResultsA total of 1 182， 167， 47， 89， 104， 203， 424 potential characteristic ions were screened from H. discus hannai， H. ruber， H. laevigata， H. ovina， H. diversicolor， H. asinina and H. iris， respectively. And 9 characteristic ions were selected. The precision， stability and repeatability of the 9 characteristic ions in the established identification method met the requirements. Different original Haliotidis Concha and its counterfeits could detect their own characteristic ions， including m/z 631.83-886.48（double charge） and m/z 631.83-443.74（double charge） of H. discus hannai， m/z 699.28-232.11（double charge） and m/z 699.28-544.27（double charge） of H. ruber， m/z 535.76-752.37（double charge） and m/z 535.76-548.28（double charge） of H. laevigata， m/z 708.35-442.28（double charge） and m/z 708.35-215.14（double charge） of H. ovina， m/z 561.33-614.86（triple charge）， m/z 561.33-468.28（triple charge）， m/z 608.29-618.32（double charge） and m/z 608.29-390.21（double charge） of H. diversicolor， m/z 769.85-274.10（double charge）， m/z 769.85-532.75（double charge）， m/z 827.43-646.36（single charge）， m/z 827.43-257.12（single charge） of H. asinina， and m/z 468.24-576.29（double charge） and m/z 468.24-505.26（double charge） of H. iris. ConclusionIn this study， a total of 9 characteristic ions are screened from 6 kinds of original Haliotidis Concha and its counterfeits， and a specific identification method is established， which is helpful to solve the limitations of the existing quality evaluation methods of Haliotidis Concha， and provide a basis for the production， circulation and medication quality.

ObjectiveTo establish a method for the identification of Haliotidis Concha and its counterfeits， and to improve its quality evaluation method. MethodsA total of 17 batches of Haliotis discus hannai， 4 batches of H. ruber， 3 batches of H. laevigata， 3 batches of H. ovina， 3 batches of H. diversicolor， 3 batches of H. asinina， 3 batches of H. iris were collected. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive-Orbitrap-MS/MS） was used to analyze the hydrolysates of different original Haliotidis Concha and its counterfeits， and the potential characteristic ions of each species were screened by Venn diagram. UPLC-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS） was used to validate the characteristic ions， and the specific detection method of the characteristic ions was established. ResultsA total of 1 182， 167， 47， 89， 104， 203， 424 potential characteristic ions were screened from H. discus hannai， H. ruber， H. laevigata， H. ovina， H. diversicolor， H. asinina and H. iris， respectively. And 9 characteristic ions were selected. The precision， stability and repeatability of the 9 characteristic ions in the established identification method met the requirements. Different original Haliotidis Concha and its counterfeits could detect their own characteristic ions， including m/z 631.83-886.48（double charge） and m/z 631.83-443.74（double charge） of H. discus hannai， m/z 699.28-232.11（double charge） and m/z 699.28-544.27（double charge） of H. ruber， m/z 535.76-752.37（double charge） and m/z 535.76-548.28（double charge） of H. laevigata， m/z 708.35-442.28（double charge） and m/z 708.35-215.14（double charge） of H. ovina， m/z 561.33-614.86（triple charge）， m/z 561.33-468.28（triple charge）， m/z 608.29-618.32（double charge） and m/z 608.29-390.21（double charge） of H. diversicolor， m/z 769.85-274.10（double charge）， m/z 769.85-532.75（double charge）， m/z 827.43-646.36（single charge）， m/z 827.43-257.12（single charge） of H. asinina， and m/z 468.24-576.29（double charge） and m/z 468.24-505.26（double charge） of H. iris. ConclusionIn this study， a total of 9 characteristic ions are screened from 6 kinds of original Haliotidis Concha and its counterfeits， and a specific identification method is established， which is helpful to solve the limitations of the existing quality evaluation methods of Haliotidis Concha， and provide a basis for the production， circulation and medication quality.

ObjectiveTo explore the quantity-quality transfer process of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（Haliotis discus hannai） by analyzing the physical phase and compositional changes， so as to provide references for the effective control of its quality. MethodsA total of 20 batches of Haliotidis Concha（H. discus hannai） from different habitats were collected and prepared into corresponding calcined products and standard decoction， and the content of CaCO₃ of the three samples were determined and the extract yield and transfer rate of CaCO₃ were calculated. The changes in elemental composition and their relative contents were investigated by X-ray fluorescence spectrometry（XRF）， X-ray diffraction（XRD） was used to study the changes in the phase compositions of the three samples and to establish their respective XRD specific chromatogram. Fourier transform infrared spectrometry（FTIR） was used to study the changes in the chemical composition and content changes of the three samples and to establish their respective FTIR specific chromatogram， while combining hierarchical cluster analysis（HCA）， principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） to find the common and differential characteristics， in order to explore the quantity-quality transfer relationship in the preparation process of standard decoction of Haliotidis Concha（H. discus hannai）. ResultsThe CaCO₃ contents of the 20 batches of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（H. discus hannai） were 93.87%-98.95%， 96.02%-99.97% and 38.29%-51.96%， respectively， and the extract yield of standard decoction was 1.71%-2.37%， and the CaCO₃ transfer rate of decoction pieces-standard decoction was 0.68%-1.27%. XRF results showed that the elemental species and their relative contents contained in Haliotidis Concha and its calcined products had a high degree of similarity， and although there was no obvious difference in the elemental species contained in decoction pieces and standard decoction， the difference in the relative contents was obvious， which was mainly reflected in the decrease of the relative content of element Ca and the increase of the relative content of element Na. XRD results showed that Haliotidis Concha mainly contained CaCO₃ of aragonite and calcite， while calcined Haliotidis Concha only contained CaCO₃ of calcite， and standard decoction mainly contained CaCO₃ of calcite and Na₂CO₃ of natrite. FTIR results showed that there were internal vibrations of O-H， C-H， C=O， HCO₃^- and CO₃^2- groups in Haliotidis Concha， while O-H， HCO₃^- and CO₃^2- groups existed in the calcined products and standard decoction. ConclusionThe changes of Haliotidis Concha and calcined Haliotidis Concha are mainly the increase of CaCO₃ content， the transformation of CaCO₃ aragonite crystal form to calcite crystal form and the absence of organic components after calcination， and the changes of calcined products and standard decoction are mainly the decrease of CaCO₃ content and the increase of Na₂CO₃ relative content. The method established in the study is applicable to the quality control of the shellfish medicines-decoction pieces- standard decoction， which provides a new idea for the study of quality control of dispensing granules of shellfish medicines.

ObjectiveTo explore the quantity-quality transfer process of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（Haliotis discus hannai） by analyzing the physical phase and compositional changes， so as to provide references for the effective control of its quality. MethodsA total of 20 batches of Haliotidis Concha（H. discus hannai） from different habitats were collected and prepared into corresponding calcined products and standard decoction， and the content of CaCO₃ of the three samples were determined and the extract yield and transfer rate of CaCO₃ were calculated. The changes in elemental composition and their relative contents were investigated by X-ray fluorescence spectrometry（XRF）， X-ray diffraction（XRD） was used to study the changes in the phase compositions of the three samples and to establish their respective XRD specific chromatogram. Fourier transform infrared spectrometry（FTIR） was used to study the changes in the chemical composition and content changes of the three samples and to establish their respective FTIR specific chromatogram， while combining hierarchical cluster analysis（HCA）， principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） to find the common and differential characteristics， in order to explore the quantity-quality transfer relationship in the preparation process of standard decoction of Haliotidis Concha（H. discus hannai）. ResultsThe CaCO₃ contents of the 20 batches of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（H. discus hannai） were 93.87%-98.95%， 96.02%-99.97% and 38.29%-51.96%， respectively， and the extract yield of standard decoction was 1.71%-2.37%， and the CaCO₃ transfer rate of decoction pieces-standard decoction was 0.68%-1.27%. XRF results showed that the elemental species and their relative contents contained in Haliotidis Concha and its calcined products had a high degree of similarity， and although there was no obvious difference in the elemental species contained in decoction pieces and standard decoction， the difference in the relative contents was obvious， which was mainly reflected in the decrease of the relative content of element Ca and the increase of the relative content of element Na. XRD results showed that Haliotidis Concha mainly contained CaCO₃ of aragonite and calcite， while calcined Haliotidis Concha only contained CaCO₃ of calcite， and standard decoction mainly contained CaCO₃ of calcite and Na₂CO₃ of natrite. FTIR results showed that there were internal vibrations of O-H， C-H， C=O， HCO₃^- and CO₃^2- groups in Haliotidis Concha， while O-H， HCO₃^- and CO₃^2- groups existed in the calcined products and standard decoction. ConclusionThe changes of Haliotidis Concha and calcined Haliotidis Concha are mainly the increase of CaCO₃ content， the transformation of CaCO₃ aragonite crystal form to calcite crystal form and the absence of organic components after calcination， and the changes of calcined products and standard decoction are mainly the decrease of CaCO₃ content and the increase of Na₂CO₃ relative content. The method established in the study is applicable to the quality control of the shellfish medicines-decoction pieces- standard decoction， which provides a new idea for the study of quality control of dispensing granules of shellfish medicines.

Objective To compare the effectiveness and safety of semaglutide with dulaglutide in patients diagnosed with type 2 diabetes.Methods A multicenter retrospective cohort study was conducted to include patients with type 2 diabetes who received semaglutide or dulaglutide treatment at three hospitals between April 2021 and July 2023 in the study.The patients were divided into the semaglutide group(SEMA group)and the dulaglutide group(DULA group)based on their treatment.Propensity score matching was used to pair the two groups in a 1:1 ratio,aligning them based on baseline characteristics such as gender,age,body mass index,blood glucose levels,duration of diabetes,and complications.Various parameters including fasting blood glucose,2-hour postprandial blood glucose,glycosylated hemoglobin(HbA1c),serum creatinine,urea nitrogen levels,estimated glomerular filtration rate(eGFR),urinary albumin/creatinine ratio(UACR),and occurrences of adverse reactions were assessed at 3,6,9,and 12 months after the treatment.Results After propensity score matching,98 patients were included in both the SEMA and DULA groups,showing no statistically significant differences in baseline characteristics between the groups(P＞0.05).At each follow-up point,the fasting blood glucose,2-hour postprandial blood glucose,and HbA1c levels of both groups showed a significant decrease compared to the baseline(P≤0.05).The inter-group comparison revealed no statistically significant differences in the changes in fasting blood glucose,2-hour postprandial blood glucose,and HbA1c levels between the two groups(P＞0.05).At the 6th month,the SEMA group exhibited a statistically significant higher rate of HbA1c＜7％compared to the DULA group(P＜0.05).In the SEMA group,serum creatinine and urea nitrogen decreased significantly at the 6th month compared to baseline,while eGFR showed an increase at the 3rd and 6th month,and UACR decreased,all with statistical significance(P＜0.05).In the DULA group,there was a statistically significant increase in serum creatinine and decrease at the 3rd and 6th months in eGFR,respectively.Additionally,urea nitrogen levels decreased significantly at the 9th month,all differences were statistically significant(P＜0.05).The inter-group comparison revealed that at the 3rd and 6th month,the SEMA group exhibited a greater reduction in serum creatinine levels compared to the DULA group.Additionally,the SEMA group demonstrated a more pronounced increase in eGFR levels than the DULA group,with statistical significance(P＜0.05).At the 6th month,the SEMA group exhibited a significantly greater decrease in UACR and a significantly lower incidence of renal insufficiency compared to the DULA group(P＜0.05).There were no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Semaglutide and dulaglutide can significantly improve blood glucose control,exhibit comparable effectiveness and safety in lowering blood glucose levels,and semaglutide has a potentially protective effect on renal function.

Objective:To investigate the effect of GRIM-19 on the resistance of carcinoma cells to the chemotherapeutic agent docetaxel in the treatment of PCa.Methods:Using siRNA technology to interfere with the gene expression in PCa cells,we estab-lished a model of GRIM-19 overexpression/knockdown in PCa cells.We investigated the effect of different expression levels of GRIM-19 on docetaxel-induced death of the PCa cells by qPCR,Western blot and flow cytometry,and assessed the value of GRIM-19 in re-ducing the chemotherapy-resistance of PCa cells.Results:GRIM-19 was down-regulated in PCa tissues and cells.Knockout of GRIM-19 significantly decreased the expression of siGRIM19 in the PC-3 and LNCaP cells,and reduced their death rate when treated with docetaxel compared with the control group.The expressions of GRIM-19 mRNA and protein were remarkably upregulated after transfection with GRIM-19,and the overexpressed GRIM-19 promoted the death of the PC-3 and LNCaP cells treated with docetaxel in a dose-dependent manner.Flow cytometry analysis showed a lower apoptosis rate of PC-3-R cells than that of PC-3 cells at different time points of docetaxel-induction at different doses.Conclusion:GRIM-19 is a PCa suppressor gene with a significant facilitating effect on the apoptosis of PCa cells,and the overexpression of GRIM-19 promotes docetaxel-induced PCa cell death and improves the sensitivity of chemotherapy.

Objective This study aims to investigate the therapeutic effect and mechanism of Naoxinqing on non-alcohol fatty liver disease (NAFLD) induced by a high-fat diet through network pharmacology,molecular docking and in vitro and in vivo experiments. Methods ApoE-/-mice were given a high-fat diet for 12 weeks to establish the NAFLD model,followed by a 12-week Naoxinqing administration. To evaluate the therapeutic effect of Naoxinqing on NAFLD induced by a high-fat diet,biochemical and histopathological experiments were performed,including assessment of blood lipids,liver function,serum inflammatory factors,as well as Hematoxylin and eosin (HE),Oil red O,and Sirius red staining of liver. Subsequently,network pharmacology and molecular docking techniques were employed to predict the key targets of Naoxinqing. Finally,the mechanism of Naoxinqing was validated by Western Blot in HepG2 cells and liver tissue. Results The results of serum biochemistry and liver tissue pathology showed that Naoxinqing can significantly improve high-fat diet-induced hepatic lipid accumulation,hepatocellular injury,and inflammation. Network pharmacology and molecular docking analysis results suggested that Naoxinqing may affect lipid metabolism through the AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1) pathway. Finally,in vitro cell experiment confirmed that the main mechanism of Naoxinqing is to activative the AMPK/SIRT1 pathway,upregulate the expression of downstream carnitine palmitoyltransferase 1 (CPT1A),promote fatty acid oxidation,and ultimately improve NAFLD. Conclusion This study demonstrated that Naoxinqing improved NAFLD by promoting fatty acid oxidation through the activation of the AMPK/SIRT1 pathway.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

Objective To observe the effects of Simo Decoction on the expressions of vasoactive intestinal peptide(VIP)and its receptor 2(VIPR2)in rats with functional dyspepsia(FD)of liver and spleen stagnation syndrome;To investigate its mechanism of action in regulating gastrointestinal motility.Methods Totally 60 SD rats were randomly divided into blank group,model group,mosapride group(0.305 mg/kg)and Simo Decoction high-,medium-and low-dosage groups(5.62,2.81,1.40 g/kg).The liver and spleen qi stagnation FD rat model was prepared by multifactorial modeling method,and the corresponding drugs were given by gavage for 14 days.The general conditions of rats in each group were observed,and body mass,gastric emptying rate and small intestine propulsion rate were measured;the histological structure of gastric antrum tissue and duodenal tissue were observed by HE staining;the positive expressions of VIP and VIPR2 in duodenal tissue were observed by immunohistochemistry;the protein and mRNA expressions of VIP and VIPR2 in duodenal tissue were detected by Western blot and RT-PCR,respectively.Results Compared with the blank group,the general condition of the rats in model group was poorer,body mass,gastric emptying rate and small intestine propulsion rate were significantly lower(P<0.01),and the protein and mRNA expressions of VIP and VIPR2 in duodenal tissue significantly increased(P<0.05,P<0.01).Compared with the model group,the body mass,gastric emptying rate and small intestine propulsion rate in Simo Decoction high-and medium-dosage groups and the mosapride group significantly increased(P<0.05,P<0.01),and the protein and mRNA expressions of VIP and VIPR2 in duodenal tissue significantly decreased(P<0.05,P<0.01).HE staining showed no significant changes in the morphology of gastric antrum and duodenum tissues.Conclusion Simo Decoction may promote gastrointestinal motility by inhibiting the expressions of VIP and VIPR2 in duodenal tissue of FD rats with liver and spleen qi stagnation,thereby improving FD.

Objective To analyze the medication law of core prescriptions and categorized prescriptions of TCM for the treatment of heart failure with preserved ejection fraction(HFpEF);To provide references for clinical prescriptions of HFpEF.Methods The clinical research literature on TCM for HFpEF was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Web of Science,Embase and Cochrane Library from establishment of the databases to November 1,2023.Data mining methods,such as complex network,prescription similarity network and community detection method were used to explore the prescription medication law of HFpEF.Results Totally 142 articles related to TCM treatment of HFpEF were included,containing 146 prescriptions and involving 162 kinds of Chinese materia medica.The most frequently used drugs were represented by Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma and Poria.The core prescription and the commonly used modified law of HFpEF treatment were obtained by complex network analysis.The core prescription consisted of Astragali Radix,Poria,Salviae Miltiorrhizae Radix et Rhizoma,Glycyrrhizae Radix et Rhizoma,Chuanxiong Rhizoma,Cinnamomi Ramulus,Descurainiae Semen Lepidii Semen,Atractylodis Macrocephalae Rhizoma,Paeoniae Radix Rubra,Ophiopogonis Radix and Angelicae Sinensis Radix.Further based on the prescription similarity network and community detection method,the basic prescriptions of the 3 major community of categorized prescription corresponding to the HFpEF staging and syndrome types were obtained,and the staged diagnosis and treatment medication law with the development of the HFpEF disease course were found.Conclusion Invigorating qi and activating blood circulation,warming yang and promoting diuresis are the main therapeutic principles of HFpEF.Data mining technology provides a feasible method for the analysis of core prescriptions and categorized prescriptions for HFpEF,which can provide a basis for the diagnosis and treatment law and medication experience of HFpEF in TCM.