Effects of Codeine on Esophageal Peristalsis in Patients With Ineffective Esophageal Motility:Studies Using High-resolution Manometry

Background/Aims@#This study aims to evaluate the effects of acute codeine administration on primary and secondary esophageal peristalsis in patients with ineffective esophageal motility (IEM). @*Methods@#Eighteen IEM patients (8 women; mean age 37.8 years, range 23-64 years) were enrolled in the study. The patients underwent highresolution manometry exams, consisting of 10 single wet swallows, multiple rapid swallows, and ten 20 mL rapid air injections to trigger secondary peristalsis. All participants completed 2 separate sessions, including acute administration of codeine (60 mg) and placebo, in a randomized order. @*Results@#Codeine significantly increased the distal contractile integral (566 ± 81 mmHg · s · cm vs 247 ± 36 mmHg · s · cm, P = 0.001) andshortened distal latency (5.7 ± 0.2 seconds vs 6.5 ± 0.1 seconds, P < 0.001) for primary peristalsis compared with these parameters after placebo treatment. The mean total break length decreased significantly after codeine treatment compared with the length after placebo (P= 0.003). Codeine significantly increased esophagogastric junction-contractile integral (P= 0.028) but did not change the 4-second integrated relaxation pressure (P= 0.794). Codeine significantly decreased the frequency of weak (P= 0.039) and failed contractions (P= 0.009), resulting in increased frequency of normal primary peristalsis (P < 0.136). No significant differences in the ratio of impaired multiple rapid swallows inhibition and parameters of secondary peristalsis were detected. @*Conclusions@#In IEM patients, acute administration of codeine increases contraction vigor and reduces distal latency of primary esophageal peristalsis, but has no effect on secondary peristalsis. Future studies are required to further elucidate clinical relevance of these findings, especially in the setting of gastroesophageal reflux disease with IEM.

Impact of Esophageal Motility on Microbiome Alterations in Symptomatic Gastroesophageal Reflux Disease Patients With Negative Endoscopy: Exploring the Role of Ineffective Esophageal Motility and Contraction Reserve

Background/Aims@#Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. @*Methods@#We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. @*Results@#Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp.and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. @*Conclusions@#In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.

Influence of Qishen Yiqi Guttate Pills on the Clinical Efficacy of Patients with Acute Myocardial Infarction After Percutaneous Coronary Intervention / 广州中医药大学学报

Objective To observe the influence of Qishen Yiqi Guttate Pills(mainly composed of Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Notoginseng Radix et Rhizoma,and Dalbergiae Odoriferae Lignum)on the clinical efficacy of patients with acute myocardial infarction after percutaneous coronary intervention(PCI).Methods Sixty post-PCI patients with acute myocardial infarction of qi deficiency and blood stasis type who met the inclusion criteria were randomly divided into a treatment group and a control group,with 30 patients in each group.The control group was treated with conventional western medicine,and the treatment group was treated with Qishen Yiqi Guttate Pills on the basis of treatment for the control group.The course of treatment for the two groups lasted for 3 months.The changes of cardiac function indicators and serum levels of hypersensitive C-reactive protein(hs-CRP)and N-terminal B-type natriuretic peptide precursor(NT-pro BNP)were observed before and after the treatment in the two groups,and the incidence of cardiovascular adverse events during the treatment in the two groups were also compared.Results(1)After treatment,the serum hs-CRP and NT-pro BNP levels of patients in the two groups were significantly decreased(P＜0.05)and the left ventricular ejection fraction(LVEF)was significantly increased(P＜0.05)compared with those before treatment.And the effects on lowering the levels of serum hs-CRP and NT-pro BNP and on increasing LVEF of the treatment group were significantly superior to those of the control group,the differences being statistically significant(P＜0.05).(2)During the treatment period,the incidence of cardiovascular adverse events in the treatment group was 6.67%(2/30),which was significantly lower than 26.67%(8/30)of the control group,and the difference was statistically significant when comparing the two groups(P＜0.05).Conclusion Qishen Yiqi Guttate Pills can effectively improve cardiac function,decrease serum hs-CRP and NT-pro BNP levels,and reduce the occurrence of adverse cardiovascular events in post-PCI patients with acute myocardial infarction of qi deficiency and blood stasis type.

Aging and age-related macular degeneration / 中华实验眼科杂志

With the aging of the population in modern society, the incidence of age-related diseases increases gradually, especially the age-related macular degeneration (AMD). Despite advances in treatment in recent years, AMD remains one of the leading causes of blindness and visual impairment in the elderly.At present, people tend to think that AMD is caused by the combination of aging and inflammation, which also contribute to the occurrence and development of many other age-related diseases.Although more studies have focused on the role of inflammation in AMD, aging, as an important correlate, is also deserves in-depth investigation.This article reviewed the close relationship between substance accumulation, abnormal phagocytosis, abnormal mitochondrial function and oxidative stress damage caused by aging and the occurrence and development of AMD, with a view to improving clinicians' knowledge of AMD.

Application of mitoxantrone hydrochloride tracer in radical thyroidectomy / 局解手术学杂志

Objective To study the effects of the mitoxantrone hydrochloride tracer on lymph node staining rate,lymph node tracing rate and parathyroid missection rate in radical thyroidectomy.Methods A total of 106 patients who received radical thyroidectomy in our hospital from February to August 2022 were selected and randomly divided into the control group and the observation group,with 53 cases in each group.The lymph node staining rate,continuous tracing success rate of patients were recorded,the number of dissected ymph nodes,the parathyroid missection rate of the two groups were compared,and the blood calcium and PTH before surgery and on the first and third day after surgery of the two groups were compared.Results The lymph node staining rate in the observation group was 90.1%,and the continuous tracing success rate was 100%.There were statistically significant differences in the number of dissected lymph nodes,parathyroid missection rate,blood calcium and PTH on the first day and third day after surgery between the two groups(P<0.05).Conclusion The mitoxantrone hydrochloride tracer has good safety and lymph node traceability,which can reduce the parathyroid missection rate,and is worthy of clinical promotion and application.

Research progress in targeting autophagy of traditional Chinese medicine and natural compounds to regulate atherosclerosis / 中国中药杂志

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.

Mechanism of cucurbitacin B suppresses proliferation of hepatocellular carcinoma Huh-7 cells via inducing ferroptosis / 中国药理学通报

Aim To study the effects of cucurbitacin B (Cu B) on proliferation of hepatocellular carcinoma Huh-7 cells and its mechanism. Methods CCK-8 was used to detect the survival rate of Huh-7 cells with different concentrations of Cu B. Huh-7 cells were treated with Cu B (0. 5, 1, 2 njnol; L

Esophageal Bolus Domain Pressure and Peristalsis Associated With Experimental Induction of Esophagogastric Junction Outflow Obstruction

Background/Aims@#Intrabolus pressures are important for esophageal bolus transport and may detect obstructed bolus flow. This study measured the effect esophageal outflow obstruction experimentally induce by a leg-lift protocol. @*Methods@#Twenty-five gastroesophageal reflux disease patients referred for esophageal manometry and a normal motility diagnosis were included. Supine liquid swallows were tested. Leg-lift protocol generated esophageal outflow obstruction by increasing abdominal pressure. Esophageal pressure topography and intrabolus pressure metrics were calculated. These included, (1) mid-domain bolus distension pressure during esophageal emptying (DPE, mmHg) and (2) ramp pressure (mmHg/sec), generated by compression of the bolus between the peristaltic contraction and esophagogastric junction (EGJ). @*Results@#EGJ relaxation pressure was increased by leg-lift from 13 (11-17) to 19 (14-30) mmHg (P< 0.005) and distal contractile integral also increased from 1077 (883-1349) to 1620 (1268-2072) mmHg · cm · sec (P < 0.001) as a physiological response to obstruction. All bolus pressures were increased by leg lift; DPE increased from 17 (15-20) to 27 (19-32) mmHg (P< 0.001), and ramp pressure increased from 3 (1-4) to 5 (2-9) mmHg/sec (P < 0.05). @*Conclusion@#Measuring pressures within the intrabolus domain can quantify changes related to obstruction to outflow and may serve as adjunct measures for confirming a diagnosis EGJ outflow obstruction.

Ultrasound-Guided Continuous Thoracic Paravertebral Block Improves Patient's Quality of Recovery After Open Hepatectomy: A Randomized, Double-Blind, Placebo-Controlled Trial / 中国医学科学杂志(英文版)

Background Ultrasound-guided continuous thoracic paravertebral block can provide pain-relieving and opioid-sparing effects in patients receiving open hepatectomy. We hypothesize that these effects may improve the quality of recovery (QoR) after open hepatectomy. Methods Seventy-six patients undergoing open hepatectomy were randomized to receive a continuous thoracic paravertebral block with ropivacaine (CTPVB group) or normal saline (control group). All patients received patient-controlled intravenous analgesia with morphine postoperatively for 48 hours. The primary outcome was the global Chinese 15-item Quality of Recovery score on postoperative day 7, which was statistically analyzed using Student's t-test. Results Thirty-six patients in the CTPVB group and 37 in the control group completed the study. Compared to the control group, the CTPVB group had significantly increased global Chinese 15-item Quality of Recovery scores (133.14 ± 12.97 vs. 122.62 ± 14.89, P = 0.002) on postoperative day 7. Postoperative pain scores and cumulative morphine consumption were significantly lower for up to 8 and 48 hours (P < 0.05; P = 0.002), respectively, in the CTPVB group. Conclusion Perioperative CTPVB markably promotes patient's QoR after open hepatectomy with a profound analgesic effect in the early postoperative period.

Establishment of finite element model of anterior cervical transpedicular system for reconstruction of cervical stability after subtotal resection of two segments of lower cervical spine / 中国骨伤

OBJECTIVE@#To establish the fixation model of anterior cervical transpedicular system (ACTPS) after subtotal resection of two segments of lower cervical spine(C3-C7) in order to provide a finite element modeling method for anterior cervical reconstruction.@*METHODS@#The CT data of the cervical segment (C1-T1) of a 30-year-old adult healthy male volunteer was collected. Used Mimics 10.0, Rapidform XOR3, HyperMesh 10.0, CATIA5V19 and ANSYS 14.0 to establish the three-dimensional nonlinear complete model of lower cervical spine(C3-C7) as the intact group. The number of units and nodes of the complete model were recorded. After the effectiveness of the complete model was verified, the C5 and C6 vertebral subtotal resection was performed, and the ACTPS model was established as the ACTPS group. The axial force of 75 N and moment couple of 1N·m was loaded on the upper surface of C3 in intact group and ACTPS group, the range of motion(ROM)and stress distribution in states of flexion extension, lateral flexion, rotation was compared between two groups.@*RESULTS@#There were 85 832 elements and 23 612 nodes in the complete model of lower cervical spine(C3-C7) which was established in this experiment. The stress distribution of ACTPS internal fixation model was relatively uniform. Comparing with the intact group, the overall range of motion in ACTPS group was decreased in flexion extension, lateral flexion and rotation directions, and the corresponding compensation of adjacent C3,4 segment was increased slightly.@*CONCLUSION@#The stress distribution of ACTPS fixation system is uniform, there is no stress concentration area at the joint of screw and titanium plate, and the fracture risk of internal fixation is low. It is suitable for stability reconstruction after anterior decompression of two or more cervical segments.

Investigation of metabolites of synthetic cannabinoid 4CN-MDMB-BUTINAC in vitro by liquid-chromatography-quadruple/orbitrap mass spectrometry / 药学学报

To investigate the metabolites of a new synthetic cannabinoid 3,3-dimethyl-2-[1-(4-cyanobutyl)indazole-3-formamimino]methyl butyrate (4CN-MDMB-BUTINACA) in vitro, a human liver microsome incubation model was established to analyze the metabolic biotransformation of synthetic cannabinoids using ultra-high performance liquid chromatography coupled to quadrupole-orbitrap high-resolution mass spectrometry. Nontarget metabolomic results showed that the metabolites of 4CN-MDMB-BUTINACA included hydroxylation, ester hydrolysis, ester hydrolysis with hydroxylation reaction, pentane oxidation and ester hydrolysis with pentane oxidation reaction, among which M1-a, M2 and M4 were potential metabolic markers. The research results provide a theoretical basis and technical support for the biomonitoring and metabolic characterisation of the cannabinoid 4CN-MDMB-BUTINACA.

Exploring the effects of artesunate and fuzheng huayu decoction on mitochondria in the treatment of schistosomiasis liver fibrosis / 中华肝脏病杂志

Objective: To compare the effects of artesunate (Art) and fuzheng huayu decoction on mitochondrial autophagy in the treatment of schistosomiasis liver fibrosis. Methods: Eighty C57BL/6 female mice were randomly divided into healthy control group, infection group, Art treatment group and Fuzheng Huayu Decoction treatment group, with 20 mice in each group. Mice in the infection group and treatment group were infected with 16 Schistosoma japonicum cercariae. After 6 weeks, praziquantel (300 mg/kg) was used for 2 days to kill the worms. The Art treatment group was treated with intraperitoneal injection of 100 mg/kg/day, while the Fuzheng Huayu Decoction treatment group was fed 16g of fuzheng huayu decoction per 1kg per day. After 6 weeks, fresh liver tissues of the four groups were collected. Masson staining and Western blot were used to observe the succinate dehydrogenase subunit A (SDHA) and malate dehydrogenase (MDH2), citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and target of rapamycin 1 (mTORC1) pathway involved in mitochondrial tricarboxylic acid cycle in liver tissues. The relative expression levels of adenylate activated protein kinase (AMPK) and mitochondrial autophagy pathway kinase (PINK1) were detected. Liver tissue samples were extracted from each group to detect the mitochondrial oxygen consumption rate. Two-way ANOVA was used to compare the significance and difference between two sets of samples. Results: Masson staining showed that the infection group mice had significantly higher liver fibrosis area than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group mice had lower liver fibrosis area than the infection group. Western blot analysis showed that the infection group (0.82 ± 0.05) had significantly lower relative expression of SDHA protein than the healthy control group (1.00 ± 0.05) (t = 11.23, P = 0.0035), while the Art treatment group (0.73 ± 0.05) had significantly higher relative expression of SDHA protein than the infection group (t = 10.79, P = 0.0073). However, there was no significant change in Fuzheng Huayu Decoction treatment group (0.98±0.05) (t = 1.925, P = 0.1266). The relative expression of p-AMPK protein was significantly higher in the infection group (1.15 ±0.05) than in the healthy control group (0.98 ± 0.07, t = 12.18, P = 0.0029), and the expression of p-AMPK in the Art treatment group (0.50 ± 0.05) was significantly lower than the infection group (t = 11.78, P = 0.0032). The relative protein expression of AMPK was significantly lower in the infection group (0.80 ± 0.05) than in the healthy control group (1.00 ± 0.05, t = 10.53, P = 0.0046). The expression of AMPK was significantly lower in the Art treatment group (0.54 ± 0.05) than in the infection group (T = 13.98, P = 0.0036). The relative expression of p-mTORC1 protein (0.93 ± 0.08) was not significantly different in the infection group than in the healthy control group (t = 2.28, P = 0.065), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1 protein than the infection group (t = 10.58, P = 0.029). The expression of p-mTORC1/ m-TORC1 was not significantly different in the infection group (0.98 ± 0.03) than in the healthy control group (0.97 ± 0.03, t = 0.98, P = 0.085), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1/ m-TORC1 than the infection group (t = 14.58, P = 0. 009). The relative protein expression of PINK1 was significantly lower in the infection group (0.55 ± 0.05) than in the healthy control group (1.00 ± 0.03, t = 13.49, P = 0.0011), while the Art treatment group (1.21 ± 0.05, t = 9.98, P = 0.0046) and Fuzheng Huayu Decoction treatment group (1.31 ±0.35, t = 6.98, P = 0.027) had significantly higher relative protein expression of PINK1 than the infection group. Mitochondrial function tests showed that after adding substrate complex II, the oxygen consumption of the infection group was lower than the healthy control group, while the Art treatment group and the Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. The oxygen consumption was significantly lower after adding the substrate complex III in the infection group than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. Conclusion: Art can alleviate schistosomiasis liver fibrosis by inhibiting AMPK/mTORC1 signaling pathway activity and enhancing mitochondrial oxygen consumption, autophagy and SDHA expression.

The inhibitory effect of lenvatinib plus fluvastatin on liver transplantation tumor in mice and corresponding mechanism / 中国药理学通报

Aim To explore the inhibitory effect of lenvatinib plus fluvastatin on liver transplantation tumor in mice and the mechanism.Methods Mouse model of subcutaneous liver cancer was used.Single agent of lenvatinib, single agent of fluvastatin, a combination of lenvatinib and fluvastatin and control solvent were given to four groups of mice.Tumor volume was measured.Immunohistochemistry was used to examine proliferation of tumor cells.Tunel was employed to detect the cell apoptosis.qRT-PCR and immunohistochemistry were used to measure the expression of TLR4.Western blot was employed to determine β-catenin expression.Rescue experiment was done using human hepatoma cells cultured in vitro.Results Treatment with both lenvatinib and fluvastatin significantly suppressed tumor growth in nude mice.Combined treatment significantly decreased the expressions of PNCA and increased apoptosis in tumor cells.Mechanically combined treatment synergistically suppressed the mRNA and protein expression of TLR4 which further inhibited the expression of β-catenin in hepatoma cells.Conclusions A combination of lenvatinib and fluvastatin synergistically inhibits tumor growth and promotes tumor cell apoptosis.The combination treatment significantly inhibits TLR4/β-catenin signaling pathway.

Comparative study between 3D guide plate assisted and free-hand insertion of anterior cervical transpedicular screw / 中国骨伤

OBJECTIVE@#To compare accuracy of anterior cervical pedicle screws between assist of rapid prototyping 3D guide plate and free-hand insertion, and evaluate the safety of two methods.@*METHODS@#Eight adult cervical cadaver specimens after formaldehyde immersion, including 4 males and 4 females, aged 32 to 65(40.3±5.6) years old. After X-ray examination to exclude bone damage and deformity, 4 of them (3D guide plate group) randomly selected were for CT scan to obtain DICOM format data, and the data was imported into Mimics software for model, designed the ideal entry point and nail path for anterior cervicaltranspedicular screw (ATPS). After obtaining the personalized guide plate of the nail channel, it was exported as STL data, and the individual guide plate was printed by rapid prototyping and 3D printing technology. In turn, with the assistance of 3D guide plates, one-to-one personalized ATPS screws were placed on the four lower cervical cadaver specimens. Another 4 (free-hand group) lower cervical cadaver specimens were implanted with ATPS screws using free-hand technique. All specimens were performed CT thin-layer scanning and three-dimensional reconstruction after operation. The Tomasino method was used to evaluate the safety of the screws on the CT cross-sectional and sagittal images, to determine whether there was a cortical puncture of the lower and inner edges of the pedicle. According to the CT rating results, gradeⅠandⅡwere safe, and grade Ⅲ- Ⅴ were dangerous.And the accuracy of screws was recorded and analyzed between two groups.@*RESULTS@#Two screws were inserted in each segment from C@*CONCLUSION@#The 3D printing rapid prototyping guide plate assisted insertion of the anterior cervical pedicle screw can significantly improve the accuracy and safety, and provide a theoretical basis for further clinical application.

Anti-inflammatory effect, plasma effective components and therapeutic targets of Huanglian Jiedu Decoction on ulcerative colitis mice / 中国中药杂志

This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1β, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P<0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P<0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1β, IL-6 and TNF-α were increased significantly in the model group(P<0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P<0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1β, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.

Exploration of scientific connotation of Magnoliae Officinalis Cortex after sweating based on network pharmacology / 中草药

Objective: Sweating is one of the important processing methods of traditional Chinese medicine. Some ingredient content of Magnoliae Officinalis Cortex (MOC) is changed after sweating which may cause the difference of efficacy. However, the molecular mechanism of how the changes of ingredient content of MOC affect the efficacy is not clear exactly. Based on the network pharmacology, the relationship between the changes of the ingredient content of MOC and the efficacy after sweating was studied. Methods: The major difference of chemical ingredients before and after sweating were screened out based on the literatures. Swiss Target Prediction was used to predict the potential targets of these components. The high confidence (score 0.900) genes/targets selected out by STRING database were used to construct protein-protein interactions network by using cytoscape 3.6.0. The clusterProfiler package in R was used to analyze gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway. Results: Nine different components (asimilobine, β-eudesmol, honokiol, magnatriol B, magnoflorine, magnolol, magnoloside A, reticuline, and syringin) were screened out. A total of 137 genes/targets were obtained (86 after deduplication). After GO annotation and KEGG enrichment analysis of the network, 550 GO-terms and 30 KEGG pathways were obtained. Conclusion: Through analysis, the change in the pharmacological effects of MOC after sweating is the result of the interaction between the components. The analgesic and anti-gastric ulcer effects of MOC may be mainly produced through the serotonergic synapse, arachidonic acid metabolism and calcium signaling pathway. And the changes in the content of chemical components such as magnolol, honokiol and β-eudesmol are the main reasons for the difference in the efficacy of MOC before and after sweating.

Association between serum biochemical parameters and transient ischemic attack / 中华老年心脑血管病杂志

Objective To study the association between H cy,hs-CRP,IMA and transient ischemic attack (TIA).Methods One hundred and twenty-six TIA patients were divided into low risk group (n=42),moderate risk group (n=43) and high risk group (n=43) according to their AB-CD2 score with 20 healthy subjects undergoing physical examinarion served as control group.Their clinical data were recorded and their serum Hcy,IMA and hs-CRP levels were compared.Results The serum levels of TC,TG,LDL,Hcy,IMA and hs-CRP were significantly higher while those of HDL were significantly lower in low risk group,moderate risk group and high risk group than in control group (P＜0.05),in moderate risk group and high risk group than in low risk group (P＜0.05),and in high risk group than in moderate risk group (P＜0.05).The serumlevels of Hcy,hs-CRP and IMA were positively associated with ABCD2 score in TIA patients (r=0.36,r =0.31,r =0.24,P＜0.05) but not associated with each other (P＞0.05).Multivariate logistic regression analysis showed that hyperlidemia and Hcy were the risk factors for TIA (P＜0.05,P＜0.01).Conclusion Serum Hcy,hs-CRP,IMA levels are positively associated with AB-CD2 score.Hyperlipidemia and Hcy are the risk factor for TIA.Measurement of serum Hcy,hsCRP,IMA levels is beneficial to the assessment of TIA.

Effect of ten-eleven translocation protein on the expression of amyloid precursor protein and β-site APP cleaving enzyme-1 in SH-SY5Y and IMR-32 cells in folic acid deficiency and the underlying mechanisms / 中华老年医学杂志

Objective To investigate the effect of ten-eleven translocation protein on the proliferation of human neuroblastoma cell lines SH-SY5Y and IMR 32 and the expression of amyloid precursor protein,PS1,and β site APP cleaving enzyme 1 in the absence of folic acid and possible mechanisms involved.Methods SH-SY5Y and IMR-32 cells were cultured in vitro and divided into the folic acid deficiency group (0 mg/L),the low folic acid group (1mg/L),and the normal control group (4mg/L).The MTT method was used to observe cell proliferation,and RT-PCR was adopted to detect the mRNA expression of APP,PS1,BACE1,DNMTs and TETs in the cells in real-time.Besides,we generated a stable low-level TET1 expression cell line,and compared the expression with that in a negative control group.Furthermore,the expression of fluorescent protein was observed by fluorescence inverted microscope,cell proliferation was measured by the MTT assay,and mRNA levels of TET1,APP,PS1,and BACE1 were detected by RT-PCR.Results (1) In the folic acid deficiency group and the low folic acid group,cell proliferation of SH-SY5Y after 120 h and of IMR-32 cell after 144 h significantly decreased (P＜0.001).The mRNA levels of APP,PS1,BACE1,DNMT1,DNMT3a,DNMT3b,TET1,TET2,and TET3 in SH-SY5Y cells increased (F=80.315,35.386,101.979,786.407,80.331,131.545,28.000,9.165,and 102.167,all P＜0.05);the mRNA levels of APP,PS1,BACE1,DNMT1,DNMT3b,TET1,TET2,and TET3 in IMR-32 cells also rose (F=12.283,93.669,40.815,157.234,24.835,147.594,54.794,and 73.068,all P＜0.05).(2) Generation of a stable low-level TET1 expression cell line:The mRNA level of TET1 in the low expression group (SH-SY5Y-shTET1) was 0.25± 0.02,which was significantly lower than that in the negative control group (1.00±0.09) (P=0.007);the mRNA level of TET1 in the low expression group (IMR-32-shTET1) was 0.28 ±0.07,significantly lower than that in the negative control group (1.00±0.01) (P=0.003).(3)The proliferative ability of the low expression groups (SH-SY5Y-shTET1 and IMR-32-shTET1) was significantly higher than that in the negative control group (P＜0.01).The mRNA levels of APP and BACE1 decreased (P＜0.01 or P＜0.05)Conclusion In the human neuroblastoma cell lines SH-SY5Y and IMR-32,folic acid deficiency up-regulates the expression of TETs,increases the expression of APP and BACE1 in the cells by TET protein demethylation,and inhibits cell growth.

Effects and potential mechanisms of bradykinin B2 receptor on growth and biological function of human extravillous trophoblast cells / 中华围产医学杂志

Objective To investigate the effects and its mechanisms of bradykinin B2 receptor (B2R) on the growth and function of human extravillous trophoblast cells (HTR-8/SVneo cells).Methods B2R expression plasmid (pcDNA3.1-B2R) was constructed and B2R-specific small interfering RNA (siRNA) was synthesized.HTR-8/SVneo cells were divided into four groups and transfected with pcDNA-3.1 (blank plasmid group),pcDNA3.1-B2R (B2R expression plasmid group),siRNA negative control and B2R-specific siRNA,respectively.Quantitative real-time reverse transcription-polymerase chain reaction and Western blot were used to detect the changes in the expression of B2R,matrix metalloproteinase-2,matrix metalloproteinase-9,cyclin D1 and vascular endothelial growth factor-A at both mRNA and protein levels in HTR-8/SVneo cells.Cell counting kit-8 and flow cytometry were used to detect cell activity and cell cycle,respectively.Cell migration assay and cell invasion assay were used to detect cell migration and invasion,respectively.Tube formation assay was used to evaluate the tube formation abilities of HTR-8/SVneo cells.All data were analyzed with t test.Results (1) Compared with the blank plasmid group,expression of B2R in HTR-8/SVneo cells in the B2R expression plasmid group were significantly increased at both mRNA (5.06±0.49 vs 1.00±0.28,t=7.226,P=0.002) and protein levels (1.34 ± 0.07 vs 1.00± 0.05,t=3.727,P=0.006).And the expression of B2R in HTR 8/SVneo cells transfected with B2R-specific siRNA were significantly reduced at both mRNA (0.34±0.05 vs 1.00±0.17,t=3.667,P=0.021) and protein levels (0.74±0.03 vs 1.00±0.05,t=4.097,P=0.006) comparing with the siRNA negative control group.(2) Compared with the blank plasmid group,HTR-8/SVneo cells being transfected with B2R expression plasmid showed a higher proliferation activity (1.50 ±0.03 vs 1.34± 0.04) promoting G0/G1 to S phase transition;compared with the siRNA negative control group,B2R-specific siRNA inhibited the proliferation of HTR-8/SVneo cells (1.06 ± 0.04 vs 1.20± 0.02) and arrested the cell cycle at G0/G 1 phase (all P＜0.05).(3) Compared with the blank plasmid group,B2R expression plasmid significantly increased the HTR-8/SVneo cell migration distance [(80.67±0.33) vs (41.33±5.24) μm],the number of cells penetrating matrigel gel (360.70 ±12.33 vs 268.70 ±14.45) and the number of cells having tube-like structures (28.20 ± 2.47 vs 14.00± 1.67),while significantly decrease was shown in these three parameters in B2R-specific siRNA group comparing with the siRNA negative control group [HTR-8/SVneo cell migration distance:(56.00±3.51) vs (87.00±1.53) μ m,number of cells penetrating matrigel gel:143.30± 12.91 vs 252.30± 17.07;number of tube-like structures:6.25±1.49 vs 15.75 ±2.02;all P＜0.05].(4) Expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 at mRNA level,and expression of cyclin D1 and vascular endothelial growth factor-A increased in the B2R expression plasmid group than in the blank plasmid group,and decreased in the B2R-specific siRNA group than in the siRNA negative control group at both mRNA and protein levels (all P＜0.05).Conclusions B2R might enhance the activity,migration,invasion and tube formation ability of human extravillous trophoblast cells through promoting the expression of matrix metalloproteinase-2,matrix metalloproteinase-9,cyclin D1 and vascular endothelial growth factor-A.

MGST1 overexpression promotes hepatocellular carcinoma development / 基础医学与临床

Objective To investigate the expression of microsomal glutathione S-transferase 1 ( MGST1) in hepa-tocellular carcinoma ( HCC) and its significance in the development of HCC. Methods Western blot was used to measure MGST1 expression in human hepatocellular carcinoma and adjacent tissues and HCC cell lines. Further-more, shRNA targeting MGST1 was constructed and transected into MHCC97H and HCCLM3 cells to deplete MGST1 expression. MGST1 was over-expressed in SK-Hep-1 cells using pCDH lentivirus system. Cell proliferation and migration were analyzed by colony formation and Transwell migration assay, respectively. The subcutaneous xenograft model of MHCC97H cells in nude mice was established to check tumor development and mouse survival.Results MGST1 was higher in 71% (17/24) of HCC tissues compared with their adjacent liver tissues. Cell proliferation and migration were significantly decreased by MGST1 knockdown, while they were increased by MGST1 overexpression. Furthermore, mice implanted with shMGST1 MHCC97H cells exhibited retarded tumor formation and tumor progression compared with control group. Conclusions MGST1 overexpression promotes hepatocellular carcinoma development and this molecule targeted for HCC treatment.