A new pyrazine from Hypecoum erectum L / 药学学报

Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo2(OAc)4 induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.

Function of Cortactin/N-cadherin signal axis in pathological myocardial hypertrophy / 中国药理学通报

Aim To investigate the regulatory effect of Cortaetin on pathological myocardial hypertrophy induced by isoprenaline (ISO) and the underlying mechanism. Methods ISO was used to stimulate neonatal rat cardiomyocytes for 24 h, and myocardial hypertrophy model was established at the cellular level. C57BL/6 mice were injected subcutaneously with ISO for one week to establish myocardial hypertrophy model at animal level. RT-qPCR was used to detect the changes of mRNA and Western blot was used to detect the changes of relative protein content. Immunofluorescence was used to measure the subcellular location of Cortaetin and the change of its expression. The overex-pression of Cortaetin by adenovirus infection and the knockdown of Cortaetin by transfection of small interfering RNA were studied. Results On the cellular and animal levels, ISO-induced myocardial hypertrophy models were successfully established, and it was observed that ISO caused the decrease of Cortaetin and N-cadherin protein levels. Overexpression of Cortaetin could reverse the decrease of N-cadherin protein level and myocardial hypertrophy caused by ISO. Knockdown of Cortaetin showed the opposite effect. Conclusion Cortaetin, in combination with N-cadherin, may play a role in combating myocardial hypertrophy by enhancing the connections between cardiomyocytes.

Study on mechanism of hydroxy-a-sanshool on diabetic cardiomyopathy based on proteomics / 中国药理学通报

Aim To explore the mechanism of hydroxy-a-sanshool in the treatment of diabetic cardiomyopathy ( DCM) based on label-free quantitative proteomics detection technique. Methods DCM model was established by high fat diet and intraperitoneal injection of streptozotocin ( STZ) . They were divided into control group ( CON group ) , diabetic cardiomyopathy group (DCM group) and hydroxy-a-sanshool treatment group ( DCM + SAN group) . The cardiac function of mice was evaluated by echocardiography, the myocardial morphology was observed by pathology staining, the protective mechanism of hydroxy-a-sanshool on diabetic cardiomyopathy was speculated by proteomic technique , and the expression level of cAMP/PKA signaling pathway and key proteins were verified by Western blotting. Results Cardiac ultrasound and pathology staining showed that hydroxy-a-sanshool had protective effect on the heart of DCM mice. Label-free quantitative proteomic analysis was carried out between DCM + SAN group and DCM group, and 160 differential pro-teins were identified by proteomics, in which 127 proteins were up-regulated and 33 proteins were down regulated ; GO secondary functional annotations showed the biological process, molecular function and cellular component; KEGG enrichment analysis showed that cAMP signaling pathway was the most abundant; protein interaction network showed that PKA as the central node interacted with many proteins in the cAMP signaling pathway. Western blot showed that the relative expression of с AMP, PKA protein in DCM group was significantly lower than that in CON group ( P < 0. 05 ) , while the relative expression of cAMP, PKA protein in DCM + SAN group was significantly higher than that in DCM group ( P < 0. 05 ) . Conclusions Hydroxy-a-sanshool has protective effect on heart function of mice with diabetes, which plays a role through cAMP signaling pathway.

Prediction of internal fixation failure of femoral trochanteric fracture by external wall morphology / 中国骨伤

OBJECTIVE@#To investigate the relationship between the shape of the lateral wall and the early failure of internal fixation in the fracture of the femoral trochanteric region(FFT).@*METHODS@#Total 295 patients with femoral trochanteric fracture underwent internal fixation from January 2015 to January 2020 were selected. The patients were divided into two groups according to whether there was early internal fixation failure after surgery, 19 patients in the failure group and 276 patients in the normal group. Gender, affected side, age, AO classification, body mass index(BMI), preoperative hemoglobin, X-ray measurement of lower lateral wall thickness, preoperative internal diseases, intraoperative blood loss, postoperative tip apex distance(TAD), postoperative neck shaft angle, operation time and other data were compared between two groups. The shape of the lateral wall was compared between two groups, and the correlation between the shape of the lateral wall and the early internal fixation failure of femoral trochanteric fracture was analyzed.@*RESULTS@#All patients were followed up for more than 1 year. There was no significant difference between two groups in terms of intraoperative blood loss, operation time, postoperative TAD, and postoperative neck shaft angle(P>0.05). At the latest follow-up, the visual anaglue scale (VAS) of the failure group was higher than that of the normal group(P<0.01), and the Harris score of the failure group was lower than that of normal group(P<0.05). The receiver operator characteristic (ROC) curve between shape of lateral wall and failure of early internal fixation of femoral trochanteric fracture was drawn. The critical value of the midpoint lateral wall thickness was 16.5 mm, and the area under the ROC curve was 0.845;The critical value of average sidewall thickness was 16.5 mm, and the area under ROC curve was 0.838;The critical value of the axial area of the sidewall was 7.5 mm, and the area under the ROC curve was 0.826.@*CONCLUSION@#The shape of the lateral femoral wall measured by CT could be used as a predictive factor for the early failure of internal fixation of femoral trochanteric fractures. For patients at risk, more reasonable surgical plans and postoperative preventive measures should be developed.

Alkaloids from fruit of Lycium chinense var. potaninii / 中国中药杂志

Ten alkaloids(1-10) were isolated from the ethyl acetate extract of the fruit of Lycium chinense var. potaninii by silica gel, ODS, and preparative high performance liquid chromatography(HPLC), and identified by NMR and MS as methyl(2S)-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(1), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(2), 3-hydroxy-4-ethyl ketone pyridine(3), indolyl-3-carbaldehyde(4),(R)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde(5),(R)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-car-baldehyde(6), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(4-hydroxyphenyl)propanoate(7), dimethyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanedioate(8), 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoate(9), 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid(10). All the compounds were isolated from the plant for the first time. Among them, compounds 1-3 were new compounds. Compounds 1-9 were evaluated for hypoglycemic activity in vitro with the palmitic acid-induced insulin resistance in HepG2 cells. At 10 μmol·L~(-1), compounds 4, 6, 7, and 9 can promote the glucose consumption of HepG2 cells with insulin resistance.

Mechanism of active components of "Notoginseng Radix et Rhizoma-Drynariae Rhizoma" in treatment of osteoporosis based on network pharmacology and in vitro cell experiment / 中国中药杂志

The present study aimed to explore the main active components and potential mechanisms of Panax notoginseng saponins(PNS) and osteopractic total flavone(OTF) in the treatment of osteoporosis(OP) through network pharmacology, molecular docking and in vitro cell experiments, which was expected to provide a theoretical basis for clinical applications. The blood-entering components of PNS and OTF were obtained from literature search and online database, and their potential targets were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The OP targets were obtained by means of searching Online Mendelian Inheritance in Man(OMIM) and GeneCards. The common targets of the drug and disease were screened by Venn. Cytoscape was used to construct a "drug-component-target-disease" network, and the core components were screened according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened according to the node degree. GO and KEGG enrichment analysis of potential therapeutic targets were carried out by R language. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock Vina. Finally, HIF-1 signaling pathway was selected for in vitro experimental verification according to the results of KEGG pathway analysis. Network pharmacology showed that there were 45 active components such as leachianone A, kurarinone, 20(R)-protopanaxatriol, 20(S)-protopanaxatriol, and kaempferol, and 103 therapeutic targets such as IL6, AKT1, TNF, VEGFA and MAPK3 involved. PI3K-AKT, HIF-1, TNF and other signaling pathways were enriched. Molecular docking revealed that the core components had good binding ability to the core targets. In vitro experiments found that PNS-OTF could up-regulate the mRNA expression levels of HIF-1α, VEGFA and Runx2, indicating that the mechanism of PNS-OTF in treating OP may be related to the activation of HIF-1 signaling pathway, and thus PNS-OTF played a role in promoting angiogenesis and osteogenic differentiation. In conclusion, this study predicted the core targets and pathways of PNS-OTF in treating OP based on network pharmacology and carried out in vitro experimental verification, which reflected the characteristics of multi-component, multi-target and multi-pathway synergy of PNS-OTF, and provided new ideas for the future clinical treatment of OP.

Formulation of expert consensus on clinical application of external ethnic medicine: taking Baimai Ointment as an example / 中国中药杂志

The concept of ethnic medicine is divided into a broad sense and a narrow sense. The broad concept refers to the traditional medicine of the Chinese nation, and the narrow concept refers to the traditional medicine of Chinese ethnic minorities. The external medicine is one of the main forms of ethnic medicine, and it is also the important content of ethnic medicine for external use, which is widely used in clinical practice. As the theory of ethnic medicine is unique, the application methods have certain characteristics, which are the key technical parts of clinical practice. However, the existing traditional Chinese medicine consensus formulation me-thods cannot meet the needs of the consensus formulation of the external ethnic medicine. Therefore, the methods suitable for expert consensus on external ethnic medicine are required. This article took Expert opinion on clinical application of Baimai Ointment as an exa-mple, and explorde a reasonable, effective, multi-dimensional, and multi-stage method to formulate expert consensus on the external ethnic medicine. In this research, three-dimensional sources of information, including ancient classics, clinical research evidence, and expert application experiences, were systematically and scientifically collected. After organization and analysis, the information was formed into comprehensive evidence. In a formal consensus meeting, part of the recommendations reached consensus. As to the issues that did not reach agreement, in-depth interviews were used to explore the reasons for the differences and resolve the disagreements. Finally, unanimous recommendations were reached. There are common problems during the formulation process of Expert opinion on clinical application of Baimai Ointment. This study is expected to provide references for the formulation of expert consensus on other external ethnic medicine.

Effect on Danggui Shaoyao Powder on mitophagy in rat model of Alzheimer's disease based on PINK1-Parkin pathway / 中国中药杂志

This study investigated the mechanism of Danggui Shaoyao Powder(DSP) against mitophagy in rat model of Alzheimer's disease(AD) induced by streptozotocin(STZ) based on PTEN induced putative kinase 1(PINK1)-Parkin signaling pathway. The AD rat model was established by injecting STZ into the lateral ventricle, and the rats were divided into normal group, model group, DSP low-dose group(12 g·kg~(-1)·d~(-1)), DSP medium-dose group(24 g·kg~(-1)·d~(-1)), and DSP high-dose group(36 g·kg~(-1)·d~(-1)). Morris water maze test was used to detect the learning and memory function of the rats, and transmission electron microscopy and immunofluorescence were employed to detect mitophagy. The protein expression levels of PINK1, Parkin, LC3BⅠ/LC3BⅡ, and p62 were assayed by Western blot. Compared with the normal group, the model group showed a significant decrease in the learning and memory function(P<0.01), reduced protein expression of PINK1 and Parkin(P<0.05), increased protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05), and decreased occurrence of mitophagy(P<0.01). Compared with the model group, the DSP medium-and high-dose groups notably improved the learning and memory ability of AD rats, which mainly manifested as shortened escape latency, leng-thened time in target quadrants and elevated number of crossing the platform(P<0.05 or P<0.01), remarkably activated mitophagy(P<0.05), up-regulated the protein expression of PINK1 and Parkin, and down-regulated the protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05 or P<0.01). These results demonstrated that DSP might promote mitophagy mediated by PINK1-Parkin pathway to remove damaged mitochondria and improve mitochondrial function, thereby exerting a neuroprotective effect.

Changes in corneal biomechanics after small incision lenticule extraction and femtosecond laser-assisted laser in situ keratomileusis evaluated by corneal visualization Scheimpflug technology / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the changes in corneal biomechanics of patients with moderate refractive error after receiving small-incision lenticule extraction(SMILE)and femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)using the corneal visualization Scheimpflug technology(Corvis ST).METHODS:Prospective cohort study. A total of 65 moderate myopia patients(65 eyes)who were scheduled to undergo refractive surgery at the Ophthalmic Refractive Surgery Center of the Ningxia Eye Hospital from November 2020 to November 2021 were included in the study, and there were 30 eyes in the SMILE group and 35 eyes in the FS-LASIK group. The changes in corneal biomechanical parameters, including integrated radius(IR), inverse concave radius(ICR), deformation amplitude ratio 2mm(DAR2), stiffness parameter at first applanation(SP-A1), ambrosio relational thickness(ARTh)and the central curvature radius at highest concavity(HC-Radius)were observed by Corvis ST between both groups preoperatively and 1 and 3mo postoperatively.RESULTS: There were no statistical significance in biomechanical parameters between two groups of patients 1 and 3mo postoperatively(P&#x0026;#x003E;0.05). IR, ICR and DAR2 of each groups of patients 1 and 3mo postoperatively were significantly increased than those preoperatively, and SP-A1, ARTh and HC-Radius were significantly decreased than those preoperatively(all P&#x0026;#x003C;0.05). The biomechanical parameters at 1mo and 3mo postoperatively showed no statistical significance(P&#x0026;#x003E;0.05). In addition, a positive correlation was found between central corneal thickness(CCT)and ARTh and SP-A1 of the two groups of patients at 3mo postoperatively(FS-LASIK group: r=0.727, 0.819, SMLIE group: r=0.683, 0.434, all P&#x0026;#x003C;0.05), while a negative correlation was found between CCT and IR and ICR at 3mo postoperatively.(FS-LASIK group: r=-0.697, -0.622, SMLIE group: r=-0.447, -0.491, all P&#x0026;#x003C;0.05).CONCLUSION:For patients with moderate myopia, both SMILE and FS-LASIK can reduce corneal biomechanical stability. Both surgeries showed no significant differences in the effect on biomechanical, and the biomechanical has been stabilized at 1mo postoperatively. A correlation was found between postoperative CCT and ARTh, SP-A1, IR and ICR.

Experimental study on the structural and functional changes of the retinal tissue induced by intense blue light irradiation in rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the structural and functional changes of retinal tissue in rats after different duration of intense blue light irradiation.METHODS: A total of 48 healthy 8-week-old SD male rats were selected and randomly divided into the control group(n=12)and 3, 6 and 12h experimental groups(n=36). The rats in the control group received natural light, and the rats in the experimental groups received blue light with a wavelength of 465±5nm and the illumination of 1000±100lx for 3, 6, and 12h each day. Optical coherence tomography(OCT), fundus fluorescein angiography(FFA)and haematoxylin-eosin(HE)staining of paraffin pathological section were used to observe the changes of the retinal thickness, retinal tissue structure and the function in different directions and layers.RESULTS: The OCT results showed that the retinal thickness in the superior, inferior, nasal, and temporal sides of rats in different groups was statistically significant(P&#x0026;#x003C;0.05), and there was no statistical significant difference between the control group and the 3h experimental group in the total retinal thickness(P&#x0026;#x003E;0.05), while the differences between any other two groups were statistically significant(P&#x0026;#x003C;0.05); The mean total retinal thickness, internal limiting membrane(ILM)-inner nuclear layer(INL)thickness, outer plexiform layer(OPL)-outer segment(OS)thickness and retinal pigment epithelium(RPE)of rats in each group were statistically significant(P&#x0026;#x003C;0.05), and the mean total retinal thickness and OPL-OS thickness were statistically significant between any two groups(P&#x0026;#x003C;0.05). The ILM-INL thickness of rats in the control group and 3 and 12h experimental groups was statistically significant(P&#x0026;#x003C;0.05), and the thickness of RPE layer in the 12h experimental group was statistically different from that of the 3 and 6h experimental groups(P&#x0026;#x003C;0.05). FFA results showed that there was no obvious fluorescence leakage in the fundus of rats in the control group and the 3h experimental group, while there was obvious fluorescence leakage and hyperfluorescence in the retina of the 6 and 12h experimental groups, and the background fluorescence of choroid was enhanced. HE staining showed the atrophy and apoptosis of cells in the optic cell layer, and some lightly stained nucleus. In addition, RPE layer showed atrophy and thinned with the increase of light time, and there was significant difference in the number of the optic cells between the control group and experimental group(P&#x0026;#x003C;0.05).CONCLUSION: The intense blue light irradiation could cause thinning of the retina in rats, with varying degrees of thinning in different layers of the retina. It could also led to decrease and even disappearance of the number of cells in the visual cell layer, the focal atrophy of the RPE layer, and the change of vascular permeability. With the extension of the light time, the structural and functional changes in retinal tissue became more obvious.

Relationship between Fok polymorphism of vitamin-D receptor gene and hypertensive disorder complicating pregnancy in Han nationality of Qinghai province / 解剖学报

[ Abstract] Objective To investigate the relationship between single nucleotide polymorphism (SNP) Fok (rs2228570 / rs10735810) of vitamin D receptor (VDR) gene and hypertensive disorder complicating pregnancy (HDCP) in Han nationality women of Qinghai province. Methods A total of 137 Han nationality HDCP subjects (HDCP group) and 146 Han nationality normal pregnant subjects (control group) were selected from Qinghai province. The Fok polymorphism typing in HCDP group and control group was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) . The mutation was confirmed by sequencing. SPSS 19. 0 statistical software was used to test whether there were significant differences between two groups in general clinical data, genotype and allele frequency distribution. Results The frequency of FF Ff ff genotype of Fok in HDCP group and control group were 51. 82%, 37. 96%, 10. 22% and 34. 93%, 43. 15%, 21. 92% respectively (

Baicalin inhibits streptozotocin-induced neuroinflammation in Alzheimer' s disease rat model by TLR4/MyD88/NF-κB pathway / 中国药理学通报

Aim To investigate the effects of baicalin on the inflammatory response and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD 88)/nuclear factor kappa B (N F-K B) signaling pathway in Alzheimer' s disease (AD) rat model induced by lateral ventricular injection of streptozotocin (STZ). Methods The AD animal model was constructed by lateral ventricular injection of STZ in SD rats, and divided into sham operation group, model group, low-dose (60 mg

Influencing factors of survival benefit of patients after radical cystectomy and its correlation with preoperative AAPR / 国际外科学杂志

Objective:To investigate the influencing factors of survival benefit of patients after radical cystectomy and its correlation with preoperative albumin-to-alkaline phosphatase ratio (AAPR).Methods:The clinical data of 116 patients after radical cystectomy were retrospectively analyzed from January 2011 to January 2020 in Handan First Hospital. The influencing factors of survival benefit of patients after radical cystectomy were analyzed and the correlation between preoperative AAPR and overall survival time were evaluated. Kaplan-Meier method was used for survival analysis, and Log-rank test was used for comparison between groups. Cox proportional regression model was used to analyze the influencing factors of survival and prognosis and the correlation with preoperative AAPR. Trend Chi-square test was used to evaluate the level of preoperative AAPR.Results:Univariate Cox regression analysis showed that age, tumor diameter, pT stage, pN stage, histopathological grade, hydronephrosis, postoperative adjuvant chemotherapy and preoperative AAPR level were related to the overall survival time of patients after radical cystectomy( P<0.05). Multivariate Cox regression analysis showed that in calibration model Ⅰ and Ⅱ, the risk of death in high AAPR group was 0.351 and 0.433 times higher than low AAPR group( P<0.05). The risk of death decreased to 85.9% and 84.6% for every one unit increase of preoperative AAPR. The overall survival time of patients with high AARP level were significantly longer than patients with low and medium AARP level( P<0.05). Conclusion:The survival benefit of patients after radical cystectomy was independently related to the preoperative AAPR level; the higher the preoperative AAPR level, the longer the overall survival time.

Clinical management and prognosis for descending necrotizing mediastinitis / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the clinical characteristics, treatment experiences and prognostic factors for descending necrotizing mediastinitis (DNM). Methods: A retrospective analysis was performed on the data of 22 patients with DNM diagnosed and treated in Henan Provincial People's Hospital from January 2016 to August 2022, including 16 males and 6 females, aged 29-79 years. After admission, all patients underwent CT scanning of the maxillofacial, cervical, and thoracic regions to confirm their diagnoses. Emergency incision and drainage were performed. The neck incision was treated with continuous vacuum sealing drainage. According to the prognoses, the patients were divided into cure group and death group, and the prognostic factors were analyzed. SPSS 25.0 software was used to analyze the clinical data. Rusults: The main complaints were dysphagia (45.5%, 10/22) and dyspnea (50.0%, 11/22). Odontogenic infection accounted for 45.5% (10/22) and oropharyngeal infection accounted for 54.5% (12/22). There were 16 cases in the cured group and 6 cases in the death group, with a total mortality rate of 27.3%. The mortality rates of DNM typeⅠand typeⅡwere respectively 16.7% and 40%. Compared with the cured group, the death group had higher incidences for diabetes, coronary heart disease and septic shock (all P<0.05). There were statistically significant differences between the cure group and the death group in procalcitonin level (50.43 (137.64) ng/ml vs 2.92 (6.33) ng/ml, M(IQR), Z=3.023, P<0.05) and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score (16.10±2.40 vs 6.75±3.19, t=6.524, P<0.05). Conclution: DNM is rare, with high mortality, high incidence of septic shock, and the increased procalcitonin level and APACHE Ⅱ score combined diabetes and coronary heart disease are the poor prognostic factors for DNM. Early incision and drainage combined with continuous vacuum sealing drainage technique is a better way to treat DNM.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(Ⅲ): classification of granule dissolving behaviors / 中国中药杂志

Solubility is an important sensory quality attribute of traditional Chinese medicine(TCM) granules. In this paper, 90 batches of granules(30 batches of TCM formula granules, 30 batches of Chinese patent medicine granules and 30 batches of Japanese Kampo granules) were used as the research objects. The turbidity sensor was used to characterize the turbidity curve of the granule dissolution process. The classification system of granule dissolution behaviors was constructed from three dimensions: dissolution degree, equilibrium time, and dissolution mechanism. According to the equilibrium time, the granule dissolution rates were divided into three categories : faster(<100 s), general(101-300 s) and slow(>301 s). According to the turbidity curve profile, the granule dissolution mechanisms were classified into dissolution-controlled type(α-type), dispersion-controlled type(β-type), and dispersion-controlled type followed by dissolution-controlled type(γ-type). The proportion of TCM formula granules, Chinese patent medicine granules and Japanese Kampo granules with complete dissolution or slight turbidity at the end of dissolution was 46.7%, 96.7%, and 10.0%. The proportion of TCM formula granules, Chinese patent medicine granules, and Japanese Kampo granules with faster dissolution rates(<100 s) was 23.3%, 26.7%, and 40.0%. The average dissolution rate of Japanese Kampo granules was faster than that of TCM formula granules, and it was slightly faster than the average dissolution rate of Chinese patent medicine granules. The dissolution mechanism of Chinese patent medicine granules was mainly α-type, while that of Japanese Kampo granules was mainly β-type, and the three types of dissolution mechanisms of TCM formula granules accounted for a relatively average. The purpose of improving the solubility and dispersion of granules can be achieved by combining the comprehensive application of various functional excipients with the small dosage of Japanese Kampo granules and the wide addition scope of excipients. In the process of transforming TCM compound prescriptions into formulas, there is still much room for innovation in formula excipients and process optimization.

Protective effect of Liujing Toutong Tablets on rats with permanent cerebral ischemia via NF-κB signaling pathway / 中国中药杂志

This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1β, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(β-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1β, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and β-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1β, IL-6, CGRP, and NO in rat serum, increased VEGF and β-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and β-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1β. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing β-EP levels.

Analysis of 50 cases of bloodstream infection with Listeria monocytogenes / 中国热带医学

@#Abstract: Objective　To analyze the characteristics of bloodstream infection of Listeria monocytogenes and provide basis for the diagnosis and treatment of the disease. Methods　We retrospectively analyzed the cases of Listeria monomyrhosi bloodstream infection in Peking Union Medical College Hospital (PUMCH) from April 2012 to April 2022. The age, sex, onset time, underlying disease, symptoms, diagnosis, treatment and prognosis of the patients were analyzed, as well as the changes of white blood cells (WBC), neutrophils, lymphocytes, and C-reactive protein (CRP) before and after anti-infection treatment. Results　Fifty cases of Listeria monocytogenes bloodstream infection confirmed by blood culture were involved. The age of patients ranged from 0 to 82 (43.7±20.0) years old, among whom 20.0% were over 60 years old. The onset time of patients was the highest in spring (44.0%), followed by winter (24.0%), and relatively fewer in summer and autumn (14.0%-18.0%). The median diagnosis time was 3 days (1-60 days). After the etiological diagnosis, 45 patients (90.0%) had underlying diseases or pregnancy status, and 45 patients were adjusted to the target antibacterial treatment mainly with carbapenems (48.9%) and penicillins (44.4%). The level of WBC, neutrophils, lymphocytes, monocytes, and CRP after treatment were significantly lower than those pre-treatments (P<0.05). Among all patients, 36 cases (72.0%) were treated according to the Antimicrobial Treatment Guidelines for Fever Sanford, of which 26 cases (72.2%) were discharged from the hospital, two cases died, one case was transferred to other hospitals, and 7 cases had a poor prognosis. Conclusions　Autoimmune diseases, tumor diseases, pregnant patients are susceptible to Listeria monocytogenes infection. Penicillins are the first choice for effective empiric therapy. For the patients allergic to penicillins, trimethoprim/sulfamethoxazole or meropenem could be used.

Quality evaluation of Qilong Zhuang'er oral liquid based on UHPLC-Q-exactive orbitrap MS and chemometrics analysis / 药学学报

An UHPLC-Q-exactive orbitrap MS method for the simultaneous determination of 19 chemical components in Qilong Zhuang'er oral liquid was established and the quality differences between different batches of samples was compared by chemometric analysis to provide a basis for the quality evaluation of the preparation. The contents of allantoin, L-proline, pyroglutamic acid, hordenine, adenosine, L-phenylalanine, guanosine, L-tryptophan, caffeic acid, calycosin-7-glucoside, verbascoside, isoacteoside, ononin, calycosin, 3-hydroxy-9,10-dimethoxyptercarpan, formononetin, atractylenolide III, atractylenolide II and astragaloside A were analyzed by cluster heat map, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) using Hiplot platform and MarkerlynxXS software to comprehensively evaluate the quality difference of different batches of Qilong Zhuang'er oral liquid. The 19 chemical compounds showed good linearity in their respective concentration ranges (r ≥ 0.999). The RSD of precision, repeatability and stability (24 h) tests were all less than 1.94%. The average recovery was 97.24%-102.75% (RSD < 2.74%, n = 6). The 10 batches of samples were divided into two categories by cluster heat map and PCA analysis. 3-Hydroxy-9,10-dimethoxyptercarpan, atractylenolide III, calycosin, atractylenolide II, formononetin, allantoin and caffeic acid were identified as differential markers by PLS-DA. The established multi component quantitative method of Qilong Zhuang'er oral liquid combined with chemometric analysis can provide reference for the quality evaluation of the preparation.

Effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier in vitro and in vivo / 药学学报

A BBB co-culture cell model consisting of rat brain microvascular endothelial cells (BMEC) and astrocytes (AS) was established to study the effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier (BBB) in vitro and in vivo. The barrier function of this model was evaluated by measuring the transendothelial resistance, phenol red permeability and BBB related protein expression. The permeability assay and western blot methods were performed to study the effects of Angelica dahurica coumarins on the BBB permeability and the expression of BBB related protein. The animal experiment protocols in this study were approved by the Animal Ethics Committee of Xi'an Jiaotong University (Animal Ethics No.: 2021-1329). The results showed that the established BMEC/AS co-culture model could be used to evaluate drug transport across BBB in vitro. After combined with Angelica dahurica coumarins, the transport capacity of puerarin was significantly increased in vitro and in vivo. Additionally, Angelica dahurica coumarins enhanced BBB permeability and inhibited the protein expression of P-glycoprotein (P-gp), zonula occludens-1 (ZO-1) and occludin. Angelica dahurica coumarins might increase BBB permeability by inhibiting the expression of P-gp and tight junction protein, thereby increasing the content of puerarin in brain tissue.

The effect of Jiegeng decoction on lipopolysaccharide-induced acute lung injury in mice based on metabolomics / 药学学报

One of the traditional prescriptions for treating lung diseases, Jiegeng decoction (JGT), is still unknown in terms of its chemical makeup and mechanism. In this study, Q-Exactive-Orbitrap MS technology was used to identify the chemical constituents of JGT, and metabolomics was used to examine the effect of JGT on metabolites in the lung tissue of mice with acute lung injury (ALI) model. The potential biomarkers were screened by fold change (FC) > 1.5 or FC < 0.67 and P < 0.05, and enriched for metabolic pathways. A total of 40 compounds, including triterpenoid saponins, flavonoids and glycosides, were identified by mass spectrometry analysis of JGT. All animal experiments were approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (No. TCM-LAEC2021106). The results showed that JGT improved the lung coefficient, and lung tissue morphology of mice with ALI, lowered the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in bronchoalveolar lavage fluid (BALF), and reduced myeloperoxidase (MPO) content in lung tissue. The metabolomic results showed that JGT could regulate 22 metabolites associated with ALI, among which leukotriene D4, docosapentaenoic acid, hypoxanthine, L-5-oxoproline, and other metabolites were mainly associated with the body′s inflammatory response and oxidative stress, and were enriched in the pathways of glutathione metabolism, purine metabolism, and primary bile acid biosynthesis. This study analyzed the potential mechanism of JGT in the treatment of ALI through metabolomics, providing an important theoretical basis for the clinical application of JGT.