Objective:To predict the therapeutic targets and potential mechanism of Yi medicine Tiaojing Yangyan Capsules in treating primary dysmenorrhea, menstrual disorders and oligomenorrhea using UPLC-Q-TOF-MS combined with network pharmacology.Methods:Using UPLC-Q-TOF-MS method, the chemical components in Tiaojing Yangyan Capsules were identified through automatic matching and retrieval from Waters UNIFI Chinese Materia Medica Database based on chromatographic peak retention time, precise relative molecular weight, characteristic fragment ions, and other information. TCMSP and SwissTarget Prediction databases were used to obtain chemical component targets, constructing a "drug-active component-target-disease" visual regulatory network and PPI network through databases such as GeneCards, DrugBank, TTD, PharmGKB, and Cytoscape 3.8.0 software. Metascape database was used to perform GO functional and KEGG pathway enrichment analysis on intersecting targets, and the potential mechanism of Tiaojing Yangyan Capsules in the treatment of primary dysmenorrhea was predicted.Results:Totally 67 components components were analyzed and identified from the Tiaojing Yangyan Capsules, which acted on 350 targets related to primary dysmenorrhea and menstrual disorders. The 15 main active components, including Ginsenoside Rg1, Ginsenoside Re, and Notoginsenoside Fe, targeted key proteins such as TNF, HSP90AA1, and STAT3, which would treat primary dysmenorrhea by regulating pathways such as the PI3K-Akt, FoxO, and Calcium.Conclusion:Tiaojing Yangyan Capsules may alleviate inflammatory reactions, alter hormone levels, regulate ovarian function, promote blood circulation, remove blood stasis, and regulate qi and blood through multiple components, targets, and pathways, thereby playing a preventive and therapeutic role in primary dysmenorrhea, menstrual disorders, and other conditions.

Abstract: This study aims to find out the causes for the dissolution of unqualified samples found during evaluation sampling of lansoprazole enteric-coated preparations by the laser infrared imaging system and orbitrap high resolution mass spectrometry, with suggestions for improvement. Lansoprazole enteric-coated preparations were tested by current standard, the dissolution of a batch of samples was below the limit and other items were in line with the standard. Considering that this product is unstable to acid and alkali, the following exploratory experiments were designed from different dimensions, based on the conclusion of the unannounced inspection of the company, to explore the reasons for the unqualified batch, including the influence of high-temperature and high-humidity storage environment on the key quality properties of the sample, the influence of 2-hour acid resistance test on dissolution result, the imaging of the core and the measure of coating layer thickness, the optimization of chromatographic conditions of related substances, and the analysis of the source of impurities. It was found that improper storage in circulation and poor coating process caused the low dissolution of this batch: the high-temperature and high-humidity storage environment possible in the circulation process led to the decreasing efficacy of disintegrating agent in the samples and thus the difficulty to release the active pharmaceutical ingredient fully; the coating solution could not be uniformly sprayed on the core, resulting in thin isolation layer and different thickness, which then affected the protection of the main drug against acid degradation. The above two reasons together resulted in unqualified dissolution of this batch. The overall quality of lansoprazole enteric-soluble preparation is good, but the formulation and process in some companies need to be optimized; and the temperature and humidity in the circulation process need to be controlled in strict accordance with the regulations.

Background/Aims: The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. Methods: We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. Results: A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers.The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. Conclusions We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.

Using high performance liquid chromatography and high resolution orbital trap mass spectrometry, a two-dimensional online desalting detection method was established to determine the structure of the impurities detected under the official testing conditions of lansoprazole enteric solution preparation, and a chromatographic method compatible with mass spectrometry was established to determine and presume the structure of the impurities that could not be separated by the the official testing method.The identification of impurity was to presume its structure according to the presence of impurity reference product, so as to investigate the difference of impurity spectrum of products from different manufacturers.The one-dimensional chromatographic conditions for the 2D online desalting method were the same as those in China Pharmacopoeia (2020) under relevant substances.Two-dimensional chromatography was performed on a Waters C18 T3 column (2.1 mm × 100 mm, 1.7 μm) with 0.1% formic acid in water-acetonitrile mobile phase and gradient elution.The chromatographic conditions for the compatible mass spectra were based on an Agilent Extend C18 (4.6 mm × 150 mm, 5 μm) column with mobile phase A: 25 mmol/L ammonium acetate and B: 25 mmol/L ammonium acetate-acetonitrile (1∶4) [pH adjusted to 6.5 with glacial acetic acid], with gradient elution. Nine impurities were detected by two-dimensional online desalting method, with 5 known impurities (A-E) and 4 unknown ones.14 impurities were detected by the compatible mass spectrometry method, with 9 unknown impurities (4 consistent with the results of two-dimensional online desalting method, and 5 newly detected).The structures and sources of the unknown impurities were deduced.The two detection methods of lansoprazole preparation by high-performance liquid chromatography-high resolution orbital trap mass spectrometry have guiding significance for quality control and process evaluation.

In order to compare the setting of difference coefficients in DRG point payment in different cities in Zhejiang province, the implementation rules of DRG point payment issued by 11 cities in Zhejiang province were comprehensively analyzed. It was found that the difference coefficients in different cities could be divided into three categories, including hospital coefficients alone, hospital coefficients and grade coefficients weighted, and weighted by hospital coefficients, grade coefficients, personal burden levels, case mix indexes, and head-to-time ratio. Its setting differences included four aspects: connotation composition, weight distribution, threshold value, and classification of medical institutions. The authors suggested that the adjustment cycle should be set scientifically to dynamically adjust the difference coefficient, and the scientific setting of the difference coefficient should be promoted through provincial coordination.

Objective: Pulmonary infectious diseases (PID) include viral pneumonia (VP) and pulmonary tuberculosis (PT). Mongolian medicine (MM) is an effective treatment option in China, however, the core group medicines (CGMs) in the treatment of PID and their underlying therapeutic mechanisms remain unclear. In this study, through the method of data mining, the CGMs of MM for the treatment of PID were excavated, and the possible mechanism of action of the CGMs in the treatment of PID was explored by using network pharmacology. Methods: First, 89 MM formulae for the treatment of pulmonary infectious diseases collected from Gan Lu Si Bu, Meng Yi Jin Kui, People's Republic of China Ministry of Health Drug Standards (Mongolian Medicine Volume), Standard of Mongolian Medicine Preparations in Inner Mongolia (2007 Edition), and Standard of Mongolian Medicine Preparations in Inner Mongolia (2014 Edition). The CGMs of MM for PID were excavated through association rule analysis and cluster analysis. Then, the active ingredients and potential targets of the CGMs were obtained from TCMSP, TCMIP, BATMAN-TCM databases. PID targets information was collected from OMIM, GeneCards, and DrugBank databases. The possible targets of CGMs treatment for PID were obtained by intersection. The PPI network was constructed through the STRING database, and the topology analysis of the network was performed. Through the enrichment analysis of the intersection targets by R language, the main action pathways and related target proteins of CGMs in the treatment of PID were screened out. The results were verified by molecular docking. Results: A total of 89 formulae were included, involving 164 MM herbs. The efficacy of the drugs was mainly cough-suppressing and panting-calming herbs, and heat-clearing herbs. The nature and flavor were mainly bitter and cold. The CGMs of MM to treatment of PID was excavated as the classic famous formula Sanzi Decoction (Toosendan Fructus-Chebulae Fructus-Gardeniae Fructus). A total of 28 candidate components and 237 predicted targets of CGMs were collected, and 61 common targets with PID were obtained, including key compounds such as quercetin, kaempferol, β-sitosterol and stigmastero and key targets such as VEGFA, IL6, TP53, AKT1. KEGG enrichment analysis yielded AGE-RAGE signaling pathways, IL-17 signaling pathways, and TNF signaling pathways. Molecular docking results showed that the key targets were well matched with the potential active ingredients of CGMs. Conclusion: This study found that MM commonly used cough-suppressing and panting-calming herbs in combination with heat-clearing herbs to treat PID, and the CGMs for the treatment of PID is “Toosendan Fructus-Chebulae Fructus-Gardeniae Fructus”. CGMs mainly play a role in the treatment of PID by acting on VEGFA, IL6, TP53, AKT1 and other targets, regulating AGE-RAGE signaling pathways, IL-17 signaling pathways, and TNF signaling pathways.

OBJECTIVETo observe the effects of electroacupuncture (EA) on inflammatory reaction of acute myocardial ischemia (MI) in mice, and to explore its action mechanism.

METHODSForty adult male C57BL/6 mice were randomly divided into a control group, a sham operation group, a model group and an EA group, 10 mice in each one. The model was established in the model group and EA group by ligating the left anterior descending branch of coronary artery. The mice in the EA group were treated with EA at "Neiguan" (PC 6) with 2 mA of intensity and 2 Hz /100 Hz of frequency; EA was given 30 min per treatment, once a day for totally 5 days. The mice in the control group and model group were treated with immobilization and no EA was given. The mice in the sham operation group were not treated with ligating at the left anterior descending branch of coronary artery, but the remaining procedure was identical to the model group. The electrocardiogram was recorded and △ST was calculated to evaluate the model. TTC and HE staining methods were applied to evaluate the infarct size and pathologic change of myocardial tissue, respectively. Western blot method was applied to test the protein expression levels of tumor necrosis factor-α (TNF-α), nuclear factor-κB p65 (NF-κB p65), interleukin-1β (IL-1β) and interleukin-8 (IL-8).

RESULTSCompared with the sham operation group, the S-T segments in the model group and EA group were increased obviously after modeling (both <0.01), indicating the MI model was established successfully. The TTC and HE staining results indicated, compared with the sham operation group, the model group had larger infarction size (<0.01), more myocardial fibers injury and inflammatory infiltration; compared with the model group, the infarction size of the EA group was significantly reduced (<0.01), and the myocardial fibers injury and inflammatory infiltration were improved. Compared with the control group, the protein expression levels in the sham operation group were similar (all >0.05); compared with the sham operation group, the expression levels of TNF-α, NF-κB p65, IL-1β and IL-8 were significantly increased in the model group (<0.01, <0.05); compared with the model group, the expression levels of TNF-α, NF-κB p65, IL-1β and IL-8 were significantly reduced in the EA group (all <0.05).

CONCLUSIONEA might reduce the protein expression levels of TNF-α, NF-κB p65, IL-1β and IL-8 in cardiac muscle tissue to inhibit inflammatory reaction and achieve myocardial protective effect in mice with acute myocardial ischemia.

Animals ; Electroacupuncture ; Inflammation ; therapy ; Interleukin-1beta ; metabolism ; Interleukin-8 ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Myocardial Ischemia ; therapy ; Myocardium ; pathology ; Random Allocation ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Lian Qiao Bai Du Wan was used to study the identification of Chinese patent medicine by molecular marker technique. DNA was extracted through modified CTAB method. The psbA-trnH and rbcL sequences were gradient amplified, and PCR products were ligated with the pEASY-T5 vector and then transformed into Trans1-T1 cells, respectively. Clones were selected randomly and sequenced. All sequences were analyzed by BlastN and the neighbor-joining (NJ) phylogenetic tree was constructed by MEGA 4.0. The results showed that nine kinds of medicinal materials can be identified by psbA-trnH sequences, and six kinds of medicinal materials by rbcL sequences from Lian Qiao Bai Du Wan. Molecular marker technique can stably and accurately distinguish multi-origin medicinal materials in Chinese patent medicine.

Molecular pharmacognosy has developed as a new borderline discipline. Using the method and technology of molecular pharmacognosy, a wide range of challenging problems were resolved, such as the identification of Mongolian medicinal raw materials, etiology of endangerment and protection of endangered Mongolian medicinal plants and animals, biosynthesis and bioregulation of active components in Mongolian medicinal plants, and characteristics and the molecular bases of Dao-di Herbs. So molecular pharmacognosy will provide the new methods and insights for modernization of Mongolian medicine.
Animals ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Humans ; Medicine, Mongolian Traditional ; Mongolia ; Pharmacognosy ; Plants, Medicinal ; chemistry ; classification ; genetics

Objective To investigate the clinical value of high frequency ultrasonography with E-flow imaging in the evaluation of fingertip's microcirculation changes in patients with systemic sclerosis(SSc).Methods Twenty-four SSc patients and 29 healthy subjects were involved.High frequency ultrasonography with E-flow imaging was used to observe the configuration and distribution of digital arteries in the last segment of left and right middle finger.Peak systolic velocity (PSV),end diastolic velocity (EDV),mean velocity(MV),vascular resistance index (RI) and pulsatility index(PI) of digital palmar propria arteries,nail bed arteries and finger ventral arteries were measured.Results In control group,rich blood supply was revealed within the fingertips.Digital palmar propria arteries,nail bed arteries and finger ventral arteries and their small branches were displayed clearly and continuously by E-flow imaging.While in SSc patients,the definition and continuity of fingertip's small vascular flow images were not as good as that in the control group,with the distribution of blood flow markedly reduced.compared with the control group,PSV,EDV and MV of digital palmar propria arteries,nail bed arteries,finger ventral arteries were decreased in SSc group(P＜0.01),but both RI and PI were increased(P＜0.05).There were no statistically significant differences between left and right fingertip's arteries index in normal control group (P＞0.05).But PSV,EDV and MV of left digital palmar propria arteries in SSc group were higher than that of the right(P＜0.05),whose differences bear statistic significance.Conclusions High frequency ultrasonography with E-flow imaging is sensitive and reliable to reflect fingertip's microcirculation changes and provide a new method to assess microvascular changes in SSc patients.