ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveTo explain the anti-inflammatory and analgesic effects of Corydalis Rhizoma by the means of structure-activity omics. MethodOn the basis of the previous in vitro screening study， we studied the in vivo efficacy of the alkaloids in Corydalis Rhizoma. With the targets as a bridge， the structures of chemical components in Corydalis Rhizoma were connected with the efficacy. The molecular docking of the alkaloids in Corydalis Rhizoma with the targets of inflammation and pain was carried out. According to the docking scores and the differences in the structural nucleus of Corydalis Rhizoma alkaloids， a study of structure-activity omics was carried out to summarize the rules of their connection. ResultThe alkaloids in Corydalis Rhizoma had good anti-inflammatory and analgesic effects in vivo， involving 53 chemical components and 73 targets. There were 3 074 targets associated with inflammation and pain， and 42 targets of direct action were shared by the chemical components and the disease. The protein-protein interaction （PPI） and molecular docking analysis predicted that the main active components of Corydalis Rhizoma were tetrahydropalmatine and palmatine， and the core targets were prostaglandin endoperoxide synthase 2 （PTGS2）， glutamate receptor metabotropic 5 （GRM5）， estrogen receptor 1 （ESR1）， solute carrier family 6 member 4 （SLC6A4）， and fusion oncoproteins （FOS）. According to the differences of mother nucleus， the 53 alkaloid components of Corydalis Rhizoma were classified into 8 categories， including protoberberine， berberine， and aporphine， which had high binding affinities with PTGS2， GRM5 and other targets. The relationship between the structures of Corydalis Rhizoma alkaloids and docking scores in each group showed the same law. In protoberberine， appropriate substituents with hydroxyl， alkoxy or methyl groups on the A and D rings of the parent ring were conducive to enhancing the binding activities with the two targets. In berberine， the structure containing a methyl group on position 13 had strong binding affinities with the two targets. It is hypothesized that the methyl fragment changes the binding mode between the component structure and amino acid residues， which greatly improves the binding affinity. ConclusionThis study employs the method of structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of alkaloids in Corydalis Rhizoma， and the structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.

ObjectiveTo explain the pharmacodynamic substances of Aurantii Fructus flavonoids that exert anti-inflammatory and analgesic effects using a structure-activity omics approach. MethodOn the basis of the previous in vitro pharmacological screening conducted by the research team， an in vivo pharmacological study of Aurantii Fructus flavonoids was carried out. Core targets of the anti-inflammatory and analgesic active components of flavonoids of Aurantii Fructus were identified using various network databases， including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， the Online Mendelian Inheritance in Man （OMIM）， and the Search Tool for the Retrieval of Interacting Genes/Proteins （STRING）. Computer-aided virtual screening technology was used to dock different types of Aurantii Fructus flavonoids with core targets. The key core targets with high binding activity were selected based on the comprehensive scores of each target and the active structures. Using these targets as bridges， the structures of one or more types of chemical components in Aurantii Fructus were closely linked to pharmacological effects. The structure-activity relationship between the clear pharmacodynamic compounds and their effects was explored through the binding patterns of various structures with pharmacodynamic targets. ResultAurantii Fructus flavonoids demonstrated significant anti-inflammatory and analgesic effects on dextran sulfate sodium （DSS）-induced colitis in mice， which could improve symptoms and significantly reduce the levels of inflammatory factors interleukin-6 （IL-6） and interleukin-1β （IL-1β）（P<0.05）. Twelve active components of Aurantii Fructus flavonoids were identified and categorized into nine dihydroflavonoids and three flavonoids based on their structures of the parent nuclei. Through Venn analysis， 167 anti-inflammatory and analgesic targets for Aurantii Fructus were identified. Based on degree value and molecular docking comprehensive scores， prostaglandin-endoperoxide synthase 2（PTGS2） and mitogen-activated protein kinase 3（MAPK3） were selected for further structural analysis. Structural analysis revealed that components containing glycoside structures exhibited higher binding activity with anti-inflammatory and analgesic targets. ConclusionThis study utilized a structure-activity omics approach based on in vivo pharmacodynamic experiments to analyze the material basis of the anti-inflammatory and analgesic effects of Aurantii Fructus flavonoids. The structure-activity omics approach provides new ideas and methods for elucidating the pharmacodynamic substances of Chinese medicine.

ObjectiveTo elucidate the active compounds for the anti-inflammatory and analgesic effects of Paeoniae Radix Alba from structure-activity omics. MethodOn the basis of the previous in vitro efficacy study by our research group， a mouse model of foot swelling was induced by methyl aldehyde and used to study the anti-inflammatory and analgesic effects of total glycosides of Paeoniae Radix Alba in vivo. The core targets of the active compounds for the anti-inflammatory and analgesic effects of Paeoniae Radix Alba were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Online Mendelian Inheritance in Man （OMIM）， and Search Tool for Recurring Instances of Neighbouring Genes （STRING）. Molecular docking was conducted for the total glucosides of Paeoniae Radix Alba with the core targets， and the key core targets with high binding affinity were screened out according to the comprehensive score of each target and active structure. The structure-activity relationship was analyzed with targets as a bridge through the combination of compound structures and pharmacological effects. ResultThe total glucosides of Paeoniae Radix Alba had good anti-inflammatory and analgesic effects in vivo. The core targets of 23 active components of Paeoniae Radix Alba were epidermal growth factor receptor （EGFR）， signal transducer and activator of transcription 3 （STAT3）， vascular endothelial growth factor A （VEGFA）， cellular tumor antigen p53 （TP53）， and proto-oncogene transcription factor （JUN）. According to the structure of the parent nucleus， there were 16 pinane monoterpene glycosides， 4 pinene monoterpene glycosides， 2 monoterpene lactone glycosides， and 1 monoterpene ketone. The key core targets screened out by molecular docking were EGFR and STAT3. The structure-activity analysis of the active compound structures and the key core targets showed that the introduction of ketone group and benzene ring group on the parent nucleus affected the binding activity. ConclusionThis study analyzed the material basis for the anti-inflammatory and analgesic effects of total glycosides of Paeoniae Radix Alba from structure-activity omics， providing new ideas and methods for revealing the pharmacodynamic substances in traditional Chinese medicine.

Among the supplementary applications for Chinese medicines， additional specifications of pills occupy a certain proportion. It is common situation that addition of water honey pills and water pills on the basis of honey pills. Due to the ingredients of Chinese medicine are complex， and honey may be related to the safety and effectiveness of the preparation as a special excipient. Therefore， the necessity of the change should be considered from multiple perspectives and aspects in combination with the characteristics of the pills， and the scientific and reasonable nature of the change should be proved through research. By thinking deeply of the review of the application for adding water honey pill and water pill specification supplement to honey pill， the author discusses the key contents that need to be paid attention to in pharmaceutical research of such changes， and puts forward the following suggestions：①The necessity of change should be considered in combination with clinical drug demand and benefit-risk ratio. ②Attach importance to the research on the change of process and excipient， and evaluate the impact of changes on drug safety and effectiveness. ③Strengthen quality and stability research， and select appropriate packaging materials to ensure stable and controllable sample quality after change. ④Reasonably expression of specifications and loading specifications.

Objective To explore the mechanism of Jiawei Bazhen Yimu Capsule on premature ovarian failure rats from the perspective of metabolomics.Methods Female SD rats were randomly divided into sham operation group,model group and Jiawei Bazhen Yimu Capsule low,medium and high dose groups,with 10 rats in each group.The model of premature ovarian failure was replicated by removing bilateral ovaries of rats and administered intragastrically once a day for 21 days.The serum samples of rats in each group were analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UPLC-Q-TOF-MS).Combined with multivariate statistical analysis,the effects of Jiawei Bazhen Yimu Capsule on differential metabolites in rats with premature ovarian failure were investigated.The differential metabolites identified by MELIN database or KEGG database were imported into Metaboanalyst 5.0 online platform for metabolic pathway analysis.Results A total of 18 potential differential metabolites were screened and identified.Most of the differential metabolites showed a good callback trend after intragastric administration of Jiawei Bazhen Yimu Capsule.These 18 differential metabolites were enriched into 2 metabolic pathways(Pathway Impact>0.1),which were glycerophospholipid metabolism and arachidonic acid metabolism pathways.Conclusion The therapeutic effect of Jiawei Bazhen Yimu Capsule on premature ovarian failure may be related to improving the level of differential metabolites in serum and restoring normal metabolic activities in rats.

Objective:To investigate the effect of air sterilization station on air quality control of digestive endoscopy center through a national multi-center dynamic monitoring research.Methods:This study was conducted jointly with 15 digestive endoscopy centers in different regions of China. Each center selected 2 endoscopy rooms using level 4 and level 3 digestive endoscopy techniques, one with an air sterilization station (the experimental group) and the other without the device (the control group). The concentrations of PM 5 and PM 0.5 in the rooms before and after the use of air sterilization station were detected and compared. Results:The air quality of all research units failed to reach the standard air cleanliness level 8 without using air sterilization station. After using the air sterilization station, the PM 5 concentration and PM 0.5 concentration of the experimental group in each center under dynamic conditions were lower than those of the control group, and the difference was significant ( P<0.05). The PM 5 concentration and PM 0.5 concentration in the experimental group at each center showed a decreasing trend with start-up time, with significant difference at different start-up times ( P<0.05). The PM 5 concentration could reach the air cleanliness level 8 standard 15.7 minutes after the air sterilization station started, and the PM 0.5 concentration could reach the air cleanliness level 8 standard 25.0 minutes after the air sterilization station started. Conclusion:In the dynamic environment of the digestive endoscopy center, the air sterilization station can significantly improve the air quality in the endoscopy rooms, which is worth promoting in endoscopy rooms of medical institutions of all levels.

Objective:To evaluate the effect of long-term intake of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) on the activation of hippocampal microglia in a mouse model of postoperative cognitive dysfunction (POCD).Methods:Ninety-six clean-grade healthy male C57BL/6 mice, aged 8 weeks, weighing 18-24 g, were stratified according to body weight and divided into 4 groups ( n=24 each) by a random number table method: control diet group (group C), ω-3 PUFAs group (group ω), control diet plus POCD group (group C+ P) and ω-3 PUFAs plus POCD group (group ω+ P). Mice were fed a special ω-3 PUFAs diet (DHA 0.14 g/100 g, EPA 0.03 g/100 g) for 12 weeks in group ω and group ω+ P, while mice were fed with a control diet for 12 weeks in group C and group C+ P.Tibial fracture procedures were performed under isoflurane anesthesia to develop the POCD model after 12 weeks of feeding.The fear conditioning test and Y maze test were performed on 1st and 3rd days after developing the model.The mice were sacrificed after behavioral tests, and the hippocampal tissues were removed for determination of the contents of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (by gas chromatography-mass spectroscopy), density of Iba-1 positive microglia (by immunofluorescence staining), and expression of mature brain-derived neurotrophic factor (mBDNF) and precursor brain-derived neurotrophic factor (pro-BDNF) (by Western blot), and contents of interleukin-1beta (IL-1β) and interleukin-6 (IL-6) (by enzyme-linked immunosorbent assay). Results:Compared with group C, the contents of DHA and EPA were significantly increased, the percentage of freezing time in the contextual test was increased, mBDNF/pro-BDNF ratio was increased ( P<0.05), no significant change was found in the rotation accuracy in Y maze test, density of Iba-1 positive microglia and contents of IL-1β and IL-6 in hippocampus ( P>0.05) in group ω ( P<0.05), and no significant change was found in the contents of DHA and EPA ( P>0.05), the percentage of freezing time in the contextual test and accuracy of rotation in Y maze test were decreased on 1st and 3rd days after operation, the density of Iba-1 positive microglia and contents of IL-1β and IL-6 were increased, and mBDNF/pro-BDNF ratio was decreased in group C+ P ( P<0.05). Compared with group C+ P, the contents of DHA and EPA were significantly increased, the percentage of freezing time in the contextual test and accuracy of rotation in Y maze test were increased on 1st and 3rd days after operation, the density of Iba-1 positive microglia and contents of IL-1β and IL-6 were decreased, and mBDNF/pro-BDNF ratio was increased in group ω+ P ( P<0.05). Conclusions:Long-term intake of ω-3 PUFAs can improve cognitive function in a mouse model of POCD, and the mechanism may be related to inhibition of activation of hippocampal microglia, reduction of inflammatory responses, and thus increasing the mBDNF/Pro-BDNF ratio.

ObjectiveTo investigate the effect of Jiawei Bazhen Yimu capsule on serum sex hormones， sexual organs and estrogen signaling pathway in female rats with premature ovarian failure. MethodThe key target proteins of Jiawei Bazhen Yimu capsule in the treatment of premature ovarian failure were screened out by network pharmacology analysis. Female healthy SD rats were selected, and the rat model of premature ovarian failure was established by ovariectomy. Fifty ovariectomized rats were randomly divided into a model group, an estradiol (E₂) valerate group, and Jiawei Bazhen Yimu capsule low, medium, and high-dose groups. Another 10 healthy female rats were set as a sham operation group. The sham operation group and the model group were given distilled water by gavage, and other administration groups were given corresponding doses of drugs by gavage. After 21 d, the serum hormone levels of female rats were measured, including E₂, progesterone (P), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Immunofluorescence staining (IF) was used to detect the protein expression levels of estrogen receptor 1 (ESR1), estrogen metabolism P4503A4 enzyme (CYP3A4), and P45019A1 enzyme (CYP19A1) in the uterine tissues of female rats. ResultAs compared with the model group, the serum E₂ and P levels of female rats in the Jiawei Bazhen Yimu capsule low, medium, and high-dose groups were significantly increased. Jiawei Bazhen Yimu capsule improved the endometrial status of female rats and increased positive expression of ESR1, CYP3A4, and CYP19A1 in the uterine tissues of female rats (P<0.05). ConclusionThe mechanism of Jiawei Bazhenyimu capsule in the treatment of premature ovarian failure may be related to its hormone-like effect and activation of the estrogen signaling pathway.