Study on the antitussive and expectorant activities and mechanism of platycodin D based on metabolomics method / 药学学报

In this paper, the antitussive and expectorant activity of platycodin D (PD) were studied by constructing a mouse cough induced by concentrated ammonia water and a mouse trachea phenol red excretion model. The mechanism of antitussive and expectorant effect of PD was studied by metabolomics. The animal experiment was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (approval number: JZLLSC-20220739). Then mice were randomly divided into the normal, model, positive drug, PD low-dose, PD medium-dose and PD high-dose group. The antitussive and expectorant effects of PD were evaluated using a cough mouse model induced by concentrated ammonia water and a mouse tracheal phenol red excretion model, respectively. UHPLC-LTQ-Orbitrap-MS was used to identify the metabolites of mouse lung tissue, and multivariate statistical analysis method of orthogonal partial least squares discriminant analysis (OPLS-DA) was used for metabolites profile analysis. The differential metabolites were screened by variable projected importance value (VIP) and t-test results. Pathways for enrichment of differentiated metabolites were analyzed using the MetaboAnalyst platform. The comparative method was applied to analyze the differences in mechanisms of PD, Deapio-platycodin D (DPD) and total platycosides fraction. The results showed that PD at different concentrations could significantly prolong (P < 0.05) the incubation period of cough mice induced by ammonia water, reduce the coughs frequency, and significantly increase (P < 0.05) the amount of phenol red excretion in phenol red excretion model mice. PD could regulate 6 metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism, phenylalanine metabolism, glycerophospholipid metabolism, and tyrosine metabolism to exert antitussive effect. It could also regulate 8 metabolic pathways of linoleic acid metabolism, glyoxylic acid and dicarboxylic acid metabolism, glycerol phospholipid metabolism, citric acid cycle and arachidonic acid metabolism to exert an expectorant effect. However, only linoleic acid metabolism and glycerophospholipid metabolism could be regulated by the PD, total platycosides fraction and DPD, which may be ascribed to the structural difference of the platycosides and the interaction between platycosides and the intestinal microbiota. Functional analysis showed that these metabolic pathways are closely related to the regulatory mechanisms of anti-inflammatory response, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and cell apoptosis. This study shows that PD possesses good antitussive and expectorant activities. In addition, the mechanism difference of PD, total platycosides fraction and DPD imply that the apiose in PD and the interaction between PD and intestinal microbiota could exert an important effect on the antitussive and expectorant mechanism of the platycosides.

A new suberin from roots of Ephedra sinica Stapf / 药学学报

Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT7 receptor protein expression in the cells, indicating potential antidepressant activity.

Short-term results of sleeve wrapping technique using remnant aortic wall in modified Bentall procedure / 中国胸心血管外科临床杂志

@#Objective To evaluate the short-term results of sleeve wrapping technique using remnant aortic wall in modified Bentall procedure. Methods The patients undergoing modified Bentall procedure with the remnant aortic wall as a sleeve to cover the sewing area of composite valved graft and the aortic annulus for proximal hemostasis between March 2021 and March 2022 in Shenzhen Fuwai Hospital were enrolled. Short-term results were assessed by cardiopulmonary bypass time, aortic clamping time, mechanical ventilation time, ICU stay, postoperative hospital stay, effusion drainage on the first postoperative day, left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), and follow-up results. Results A total of 14 patients were collected, including 12 males and 2 females, with a mean age of 55.33±10.57 years. There was no postoperative or follow-up death. Cardiopulmonary bypass time was 147.90±21.29 min, aortic clamping time was 115.70±15.23 min, mechanical ventilation time was 19.42±8.98 h, ICU stay was 99.08±49.42 h, and postoperative hospital stay was 16.33±2.74 d. Thoracic drainage volume was 333.33±91.98 mL on the first postoperative day. Only 2 patients required blood transfusion (4.5 U and 2 U, respectively). During the follow-up of 6.17±3.69 months, there was no death, no aortic or valve-related complications. There was statistical difference in the LVEDD between preoperation and before discharge after surgery (P＜0.001), and between half a year after surgery and before discharge after surgery (P＜0.001). There was a little decrease of LVEF before discharge after surgery compared with preoperative LVEF, but there was no statistical difference (P=0.219). There was no statistical difference in the LVEF half a year after operation compared with that before operation (P=1.000). Conclusion Sleeve wrapping technique using remnant aortic wall in modified Bentall procedure has good short-term results. This modification may be a simple, effective way in controlling proximal bleeding.

Effect of quercetin's anti-breast cancer depending on presence of estrogen receptor via down-regulating long non-coding RNA MALAT-1 and its mechanism / 中国药理学通报

Aim To investigate the molecular mechanism by which quercetin inhibits the malignant behavior of breast cancer cells. Methods Breast cancer cell lines MCF-7 and MB231 were used as the research models. Lentiviral transfection was employed to establish tumor cells with high expression of ERa and MAL-AT-1. The expression of MALAT-1 was assessed using RT-qPCR,and ERa expression was determined through Western blot. Subsequently, CCK-8 assay and colony formation assay were conducted to evaluate cell proliferation. PI staining and adenovirus transfection were performed to observe the inhibitory effects of quercetin on breast cancer cell proliferation. Results 17|3-es-tradiol ( E2 ) promoted the proliferation of MCF-7 breast cancer cells, while 5 jjunol L quercetin reversed the promoting effect of E2 on proliferation ( P 0. 05 ) . Quercetin had no effect on MB231 breast cancer cells. Overexpression of ERa significantly inhibited the pro-proliferative effect of E2 on MB231-ERa cells, and quercetin further suppressed this effect. Additionally , quercetin inhibited the expression of MALAT-1. However,this inhibitory effect was reversed by overexpression of MALAT-1, leading to enhanced cell proliferation , cell cycle progression, and clonal formation a-bility. Conclusions Quercetin exerts its anti-tumor effects on breast cancer cells by regulating MALAT-1, dependent on the presence of estrogen receptor. Quercetin shows potential as a therapeutic drug for breast cancer targeting the estrogen receptor.

Comparison of clinical features and outcomes of proliferative, fibrotic, and mixed subtypes of IgG4-related disease: A retrospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated disorder that can affect almost any organ in the human body. IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients' clinicopathological characteristics. This study aimed to compare the clinical manifestations, laboratory findings, and treatment outcomes of IgG4-RD among different subtypes.@*METHODS@#We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021. The patients were divided into three groups according to their clinicopathological characteristics: proliferative, fibrotic, and mixed subtypes. We compared demographic features, clinical manifestations, organ involvement, laboratory tests, and treatment agents across three subtypes. We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants. Moreover, risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis.@*RESULTS@#We classified the 622 patients into three groups consisting of 470 proliferative patients, 55 fibrotic patients, and 97 mixed patients, respectively. We found that gender distribution, age, disease duration, and frequency of allergy history were significantly different among subgroups. In terms of organ involvement, submandibular and lacrimal glands were frequently involved in the proliferative subtype, while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype. The comparison of laboratory tests revealed that eosinophils ( P = 0.010), total IgE ( P = 0.006), high-sensitivity C-reactive protein ( P <0.001), erythrocyte sedimentation rate ( P <0.001), complement C4 ( P <0.001), IgG ( P = 0.001), IgG1 (P <0.001), IgG4 (P <0.001), and IgA ( P <0.001), at baseline were significantly different among three subtypes. Compared with proliferative and mixed subtypes, the fibrotic subtype showed the lowest rate of relapse (log-rank P = 0.014).@*CONCLUSIONS@#Our study revealed the differences in demographic characteristics, clinical manifestations, organ involvement, laboratory tests, treatment agents, and outcomes across proliferative, fibrotic, and mixed subtypes in the retrospective cohort study. Given significant differences in relapse-free survival among the three subtypes, treatment regimens, and follow-up frequency should be considered separately according to different subtypes.

Systematic review and Meta-analysis of efficacy and safety of Kushen Gelatum combined with antibiotics in treatment of bacterial vaginosis / 中国中药杂志

This study aims to systematically evaluate the clinical efficacy and safety of Kushen Gelatum combined with antibiotics for treating bacterial vaginosis. The randomized controlled trial(RCT) of Kushen Gelatum for treating bacterial vaginosis were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, and Cochrane Library with the time interval from inception to January 2023. Data were extracted from the included RCT by 2 investigators, including the sample size, characteristics of patients, interventions and controls, outcome indicators, and adverse effects. The Cochrane collaboration network's bias risk assessment tool was used for methodolo-gical quality evaluation of the included trials. RevMan 5.4 was employed to perform the Meta-analysis. A total of 19 RCTs were inclu-ded, involving 1 980 patients with bacterial vaginosis. Meta-analysis showed that, compared with nitroimidazoles alone, Kushen Gelatum + nitroimidazoles improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.24, 95%CI[1.13, 1.36], P<0.000 01), laboratory tests(RR=1.16, 95%CI[1.06, 1.26], P=0.000 9), and clinical symptoms(RR=1.26, 95%CI[1.08, 1.46], P=0.003), and reduced the leukocyte esterase positive rate(RR=0.29, 95%CI[0.17, 0.48], P<0.000 01) and the recurrence rate(RR=0.37, 95%CI[0.23, 0.58], P<0.000 1). Compared with lincomycin antibiotics(clindamycin) alone, Kushen Gelatum + lincomycin antibiotics(clindamycin) improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.06, 1.31], P=0.003) and laboratory tests(RR=1.27, 95%CI[1.04, 1.54], P=0.02), reduced the recurrence rate(RR=0.20, 95%CI[0.05, 0.75], P=0.02), and shortened the time to relief of burning sensation(MD=-1.70, 95%CI[-2.15,-1.26], P<0.000 01), vaginal itching(MD=-0.82, 95%CI[-1.30,-0.34], P=0.000 8), and abnormal leucorrhea(MD=-1.52, 95%CI[-1.98,-1.06], P<0.000 01). Compared with nitroimidazoles + probiotics, Kushen Gelatum + nitroimidazoles + probiotics improved the total response rate in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.02, 1.36], P=0.03) and reduced the recurrence rate(RR=0.27, 95%CI[0.09, 0.76], P=0.01). Kushen Gelatum combined with antibiotics demonstrates a potential therapeutic effect on bacterial vaginosis, whereas the number and quality of the relevant clinical studies remain to be improved. The process of clinical trial should be standardized to improve the quality of evidence, so as to provide strong evidence to guide the application of Kushen Gelatum in clinical practice.

Metabolomic study on urine of chronic inflammation rats treated with Buyang Huanwu Decoction based on UPLC-Q-TOF-MS / 中国中药杂志

The study investigated the effect of Buyang Huanwu Decoction(BYHWD) on endogenous biomarkers in the urine of rats with chronic inflammation induced by lipopolysaccharide(LPS) using ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS), aiming to elucidate the molecular mechanism underlying the therapeutic effect of BYHWD on chronic inflammation from a metabolomics perspective. Male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose BYHWD groups(7.5, 15, and 30 g·kg~(-1)). The model group and BYHWD groups received tail intravenous injection of LPS(200 μg·kg~(-1)) on the first day of each week, followed by oral administration of BYHWD once a day for four consecutive weeks. Urine samples were collected at the end of the administration period, and UPLC-Q-TOF-MS was used to analyze the metabolic profiles of the rat urine in each group. Multivariate statistical analysis methods such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the effect of BYHWD on endogenous metabolites. One-way ANOVA and variable importance for the projection(VIP) were used to screen for potential biomarkers related to chronic inflammation. The identified biomarkers were subjected to pathway and enrichment analysis using MetaboAnalyst 5.0. A total of 25 potential biomarkers were screened and identified in the rat urine in this experiment. Compared with the normal group, the model group showed significant increases in the levels of 14 substances(P<0.05) and significant decreases in the levels of 11 substances(P<0.05). BYHWD was able to effectively reverse the trend of most endogenous biomarkers. Compared with the model group, BYHWD significantly down-regulated 13 biomarkers(P<0.05) and up-regulated 10 biomarkers(P<0.05). The metabolic products were mainly related to the biosynthesis of pantothenic acid and coenzyme A, tryptophan metabolism, retinol metabolism, and propionate metabolism. BYHWD has therapeutic effect on chronic inflammation induced by LPS, which may be related to its ability to improve the levels of endogenous metabolites, enhance the body's anti-inflammatory and antioxidant capabilities, and restore normal metabolic activity.

The effect of LeCompte maneuver on mid-to-long term reintervention after arterial switch operation in children with side-by-side Taussig-Bing anomaly / 中国胸心血管外科临床杂志

@#Objective    To explore the effect of LeCompte maneuver on in-hospital mortality and mid-to-long term reintervention after single-stage arterial switch operation in children with side-by-side Taussig-Bing anomaly. Methods     Clinical data of patients diagnosed with side-by-side Taussig-Bing anomaly and undergoing single-stage arterial switch operation in Shanghai Children’s Medical Center from 2006 to 2017 were retrospectively analyzed. Patients were divided into two groups based on whether LeCompte maneuver was performed: a LeCompte maneuver group and a non LeCompte maneuver group. The clinical data of two groups were compared. Results    Finally 92 patients were collected. LeCompte maneuver was performed in 32 out of 92 patients with a median age of 65.0 days and an average weight of 4.3 kg, among whom 24 (75.0%) were male. Fifteen (46.9%) patients received concomitant aortic arch repair while 12 (37.5%) patients were associated with coronary artery malformation. LeCompte maneuver was not performed in 60 patients with a median age of 81.0 days and an average weight of 4.8 kg, among whom 45 (75.0%) were male. Twenty-two (36.7%) patients received concomitant aortic arch repair while 35 (58.3%) patients were associated with coronary artery malformation. The average cardiopulmonary bypass duration of the LeCompte maneuver group showed no statistical difference from the non LeCompte maneuver group (179.0±60.0 min vs. 203.0±74.0 min, P=0.093). The in-hospital mortality of the two groups were 6 (18.8%) and 7 (11.7%), respectively, which also showed no statistical difference (P=0.364). The median follow-up period was 4.1 (1.6, 7.5) years for 79 patients with 8 lost to follow-up, and no death was observed. Kaplan-Meier curve and log-rank test showed no statistical difference in overall mid-to-long term reintervention rate (P=0.850) as well as right ventricular outflow tract and pulmonary artery reintervention rate (P=0.240) with or without LeCompte maneuver. Conclusion    Whether or not to perform LeCompte maneuver shows no statistical impact on in-hospital mortality and mid-to-long term reintervention rate of single-stage arterial switch operation for side-by-side Taussig-Bing anomaly.

Study on differential expression of Sirtuin1 in type A aortic dissection pateints at diverse ages / 中国胸心血管外科临床杂志

@#Objective    To explore the differential expression of Sirtuin1 (SIRT1) in type A aortic dissection at diverse ages. Methods    The expression of SIRT1 and monocyte chemoattractant protein-1 (MCP-1) in aortic tissue of the patients with type A aortic dissection (an aortic dissection group) and coronary heart disease (a control group) from 2019 to 2020 in the First Hospital of China Medical University was analyzed. In each group, the patients were divided into 3 subgroups according to the age (a younger subgroup, <45 years; a middle age subgroup, 45-60 years; an elderly subgroup, > Compared with the control group, SIRT1 protein expression decreased significantly in the aortic dissection group (the younger group: 0.64±0.18 vs. 1.18±0.47; the middle age group: 0.43±0.26 vs. 0.69±0.32; the elderly group: 0.31±0.24 vs. 0.45±0.29, P<0.01). The Western blotting results showed that the expression of SIRT1 protein in the aortic dissection group decreased with age (P<0.01). The MCP-1 protein expression of younger and middle age patients in the aortic dissection group was increased compared with that in the control group (the younger group: 0.65±0.27 vs. 0.38±0.22; the middle age group: 1.08±0.30 vs. 0.46±0.36, P<0.001). MCP-1 expression increased with age (P<0.01). The result of immunohistochemical staining for SIRT1 protein was similar to that of Western blotting. Conclusion    The expression of SIRT1 decreases in patients with aortic dissection disease, and declines with age. SIRT1 may play an important role in the treatment and screening of type A aortic dissection.60 years). The quantitative real-time PCR, Western blotting and immunochemical stainning were used to detect the mRNA or protein expression of SIRT1 and MCP-1. Results    A total of 60 patients were included in each group, including 79 males and 41 females. There were 20 patients in the yonger, middle age and elderly subgroups for the two groups, respectively. Compared with the control group, the expression of SIRT1 mRNA decreased in the aortic dissection group (the younger subgroup: 4.54±1.52 vs. 8.78±2.57; the middle age group: 2.70±1.50 vs. 5.74±1.07; the elderly group: 1.41±1.33 vs. 3.09±1.14, P<0.001). Meanwhile, SIRT1 mRNA in the aortic dissection group declined with age (P<0.01).

Genetic analysis of a gonadal-mosaicism BMD family with prenatal diagnosis and PGT-M / 中华检验医学杂志

Objective:To identify the pathogenic characteristics of a suspected gonadal mosaicism Becker muscular dystrophy (BMD) family, and provide provide basis for pregnancy selection of similar families.Methods:A BMD family admitted to Hunan Jiahui Genetics Hospital from June 2012 to September 2019 was systematically reviewed. The medical history and family history of the proband were checked, and multiplex ligation-dependent probe amplification was used to detect the deletion/duplication of 79 exons of the Duchenne muscular dystrophy (DMD) gene in the proband, fetuses, and parents. Moreover, potential variants were verified by combining PCR amplification, short tandom repeat polymorphic linkage analysis, and real-time fluorescence quantitative PCR. High-quality embryos are screened for transplantation after preimplantation genetic testing for monogenic (PGT-M). And amniotic fluid was collected in the second trimester for prenatal diagnostic verification.Results:According to the phenotype analysis of the proband, the initial clinical diagnosis was BMD, and the exon 45-50 deletion in DMD gene was detected. The mutation was not detected in the mother′s peripheral blood, but when she was pregnant again, the prenatal diagnosis showed that the fetus had the same deletion mutation as the proband. Neither of two vitro embryos tested by PGT-M has the deletion mutation, then single embryo transfer was performed nor was pregnancy successful. After confirmation of prenatal diagnosis during pregnancy, a normal baby girl was born by full-term cesarean section.Conclusions:This BMD family was a family with two consecutive BMD homodeletion mutations, and the mutation of the DMD gene was not detected in the peripheral blood of the proband′s mother and two embryonic cells, suggesting that the mother may be a gonad chimeric carrier of this deletion mutation. The combined application of prenatal diagnosis and PGT-M provides a reference approach to effectively avoid the birth of similar children.

Recommendations for the diagnosis and treatment of Sj?gren′s syndrome in China / 中华内科杂志

Sj?gren′s syndrome (SS) is a chronic systemic autoimmune disease characterized by lymphocyte proliferation and progressive exocrine gland damage. In addition to the impairment of salivary and lacrimal gland function, SS can present with multi-system and multi-organ involvement, accompanied by autoantibodies in serum and hyperimmunoglobulinemia. SS can be divided into primary and secondary forms based on the absence or presence, respectively, of concurrent connective tissue diseases such as systemic lupus erythematosus and rheumatoid arthritis. Based on evidence and guidelines from China and other countries, the Chinese Rheumatology Association drafted standardized criteria for the diagnosis and treatment of primary SS. The objectives were to standardize the detection and interpretation of key indicators for the diagnosis of SS, including serum anti-SSA antibody and labial gland pathology, suggest the use of the widely accepted European League Against Rheumatism (EULAR)-SS disease activity index for the evaluation of the disease, and standardize the rational management of SS patients with topical and systemic therapies.

Efficacy and safety of percutaneous left atrial appendage occlusion for nonvalvular atrial fibrillation / 中国基层医药

Objective:To investigate the efficacy and safety of percutaneous left atrial appendage occlusion in the treatment of nonvalvular atrial fibrillation.Methods:Eighty-eight patients with percutaneous left nonvalvular atrial fibrillation who received treatment in The Second Hospital of Anhui Medical University from January 2019 to January 2021 were included in this study. These patients were divided into three groups according to different anticoagulant methods: group A (percutaneous left atrial appendage occlusion), group B (livaraban), and group C (warfarin). The incidence of stroke, the incidence of bleeding events, the incidence of adverse cardiovascular events, and live and kidney function and coagulation function after 3 months of treatment were compared among the three groups.Results:There were no significant differences in the incidence of stroke and adverse cardiovascular events among the three groups ( P > 0.05). The incidence of bleeding events in groups A, B, and C was 9.3% (3/32), 15.0% (6/40), and 31.2% (5/16), respectively. There was a significant difference in the incidence of bleeding events among the three groups ( χ2 = 8.07, P = 0.001). After 3 months of treatment, there were no significant differences in prothrombin time, fibrinogen, prothrombin time-international normalized ratio, alanine aminotransferase, aspartate transaminase, and creatinine clearance among the three groups (all P > 0.05). Conclusion:Percutaneous left atrial appendage occlusion, warfarin, and rivaroxaban can prevent stroke in patients with nonvalvular atrial fibrillation. Percutaneous left atrial appendage occlusion is safer and more feasible than warfarin and rivaroxaban alone in the treatment of nonvalvular atrial fibrillation.

Status survey and countermeasures for trainees in standardized residency training of ultrasound professional base under the novel coronavirus pneumonia epidemic / 中华医学教育探索杂志

Objective:To investigate the behavior and emotion of trainees (residents) in the standardized residency training under the novel coronavirus pneumonia (NCP) epidemic, and adjust the training plan and mode of standardized residency training during the NCP epidemic according to the survey results.Methods:A real-name closed questionnaire survey was conducted among 40 residents (27 ultrasound majors and 13 other majors) in ultrasound department using the "Questionnaire Star" WeChat applet, including basic personal information, questions related to NCP, behavioral change survey, behavioral attitude survey and emotional status survey. All the collected data were further statistically analyzed by Chi-square test and rank sum test using SPSS 19.0Results:There were forty valid questionnaires and the participation rate was 100.0%. The accuracy of 24 NCP-related questions was not significantly different between residents majoring in ultrasound and other specialties [92.0%(596/648) vs. 93.6%(292/312), P>0.05]. All the residents had a good understanding of NCP. The main behaviors of going out were significantly reduced, while various behaviors of being at home were significantly increased. Their interest in learning declined. When the epidemic happened (or possibly) in the community or village they lived in, their negative emotions, such as nervousness, fear pessimism and depression, were obviously expressed. Network teaching and evaluation through WeChat public number were adopted and we guided residents to adjust their home behaviors and emotions according to the survey results. Conclusion:Under the NCP epidemic, the behaviors and emotions of residents had been extensively changed. The training center should adjust the teaching plan and mode of training in time, and provide more counselling service in psychology and learning for residents during the epidemic.

S-propargyl-cysteine delays the progression of atherosclerosis and increases eNOS phosphorylation in endothelial cells / 生理学报

The present study aimed to investigate the protective effect of S-propargyl-cysteine (SPRC) on atherosclerosis progression in mice. A mouse model of vulnerable atherosclerotic plaque was created in ApoE-/- mice by carotid artery tandem stenosis (TS) combined with a Western diet. Macrophotography, lipid profiles, and inflammatory markers were measured to evaluate the antiatherosclerotic effects of SPRC compared to atorvastatin as a control. Histopathological analysis was performed to assess the plaque stability. To explore the protective mechanism of SPRC, human umbilical vein endothelial cells (HUVECs) were cultured in vitro and challenged with oxidized low-density lipoprotein (ox-LDL). Cell viability was determined with a Cell Counting Kit-8 (CCK-8). Endothelial nitric oxide synthase (eNOS) phosphorylation and mRNA expression were detected by Western blot and RT-qPCR respectively. The results showed that the lesion area quantified by en face photographs of the aortic arch and carotid artery was significantly less, plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were reduced, plaque collagen content was increased and matrix metalloproteinase-9 (MMP-9) was decreased in 80 mg/kg per day SPRC-treated mice compared with model mice. These findings support the role of SPRC in plaque stabilization. In vitro studies revealed that 100 μmol/L SPRC increased the cell viability and the phosphorylation level of eNOS after ox-LDL challenge. These results suggest that SPRC delays the progression of atherosclerosis and enhances plaque stability. The protective effect may be at least partially related to the increased phosphorylation of eNOS in endothelial cells.

Effects of transient receptor potential vanilloid 4 inhibitor HC067047 on anxiety-like behavior in mice induced by lipopolysaccharide / 解剖学报

Objective To investigate the effect of transient receptor potential vanilloid 4 (TRPV4) inhibitor HC067047 on anxiety-like behavior in mice induced by lipopolysaccharide (LPS). Methods Totally 48 male C57BL/6 mice were randomly divided into control group (NS), model group (LPS) and drug intervention group (HC + LPS). Anxiety mouse model was established by intraperitoneal injection of 0.83 mg/kg LPS. The HC + LPS group was intraperitoneally injected with HC067047 (10 mg/kg) 30 minutes before LPS injection, and the NS group and LPS group were injected with equal volume of normal saline. Open field test and social interaction experiments were used to detect anxiety-like behaviors in each group of mice; Immunohistochemical chemistry and Western blotting were used to detect the expression of TRPV4, inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in the hippocampus. Results Immunohistochemical and Western blotting experiments showed that, compared with the NS group, the expression of TRPV4 in the hippocampus of the LPS group was significantly up-regulated (P<0.0001); In the open field test, compared with the NS group, the total distance (P < 0.0001), the distance in the central area (P<0.01) and the time of in the central area mice in the LPS group reduced significantly (P< 0.01). HC067047 intervention reversed the activities of LPS model mice total distance (P < 0.05), the distance of activities in the central area (P < 0.001) and the time of in the central area (P < 0.01); In the social interaction test, compared with the NS group, the interaction time the unfamiliar mice reduced significantly in LPS group (P<0.01), which was reversed by HC067047 treatment (P< 0.01); Western blotting detection revealed that the expression of hippocampal iNOS (P<0.05), nNOS (P < 0.001), and eNOS (P < 0.001) in the LPS group were significantly higher than the NS group, which reduced remarkably by HC067047 treatment (iNOS P < 0.05, nNOS P < 0.01 and eNOS P < 0.01). Conclusion Inhibiting the expression of TRPV4 can improve the anxiety-like behavior, and this process may be related to anti-oxidative stress.

Study on bioequivalence evaluation of dexamethasone acetate tablets in Chinese healthy volunteers / 中国临床药理学与治疗学

AIM: To assess the bioequivalence of oral dexamethasone acetate tablets between the test and reference formulations in healthy adult Chinese subjects on an empty stomach and after meals. METHODS: A randomized, open, single-dose, two-cycle double crossover bioequivalence study was followed. Twenty-four healthy subjects were included in the fasting group, and 32 healthy subjects were included in the postprandial group, taking 2 tablets (0.75 mg/tablet) of the test formulation (T) or 3 tablets (0.50 mg/tablet) of the reference formulation (R) per cycle for two cycles. The concentrations of dexamethasone acetate in human plasma were determined using liquid chromatography-mass spectrometry, and the pharmacokinetic parameters were calculated according to the non-atrial model using WinNonlin 8.0 software.The bioequivalence of both the test formulation and the reference formulation was evaluated. RESULTS: The pharmacokinetic parameters after oral administration of dexamethasone acetate tablets in a fasted state in subjects with the reference formulation are as follows: Tmax 1.13 (0.50, 4.00) and 1.00 (0.50, 5.00) h, AUC0-t (72.25±21.55) and (69.23±17.76) ng · mL

Research progress on experimental animal models of hyperuricemia / 中国药理学通报

Hyperuricemia is a chronic metabolic disease caused by purine metabolism disorder or uric acid excretion disorder. The experimental animal model of hyperuricemia is the basis for studying the pathological mechanism and drug treatment of hyperuricemia. This paper reviews the experimental animal models of hyperuricemia commonly used in drug research, and introduces the modeling principle, preparation methods, species selection and related detection techniques of the models, so as to provide reference for the application of such models in research.

Role and mechanism of glucagon-like peptide-1 in depression / 中国药理学通报

Glucagon-like peptide-1 (GLP-1) is a major hormone of incretin hormone and gut-brain axis, which is related to the control of energy homeostasis and the occurrence of obesity. In addition to suppressing appetite, GLP-1 has neuroprotective effects by acting on areas of the brain involved in stress response and mood regulation. Depression is a common mental disease, and GLP-1 is closely related to depression. This article reviews the role and mechanism of GLP-1 in depression.

Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9 / 中西医结合学报

OBJECTIVE@#To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation.@*METHODS@#Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9.@*RESULTS@#EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.@*CONCLUSION@#Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.

Hyperoxia caused intestinal metabolism disorder in mice / 中华危重病急救医学

OBJECTIVE@#To investigate the effect of hyperoxia on intestinal metabolomics in mice.@*METHODS@#Sixteen 8-week-old male C57BL/6 mice were randomly divided into hyperoxia group and control group, with 8 mice in each group. The hyperoxia group was exposed to 80% oxygen for 14 days. Mice were anesthetized and euthanized, and cecal contents were collected for untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) combined detection. Orthogonal partial least square discriminant analysis (OPLS-DA), volcano plot analysis, heat map analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the effects of hyperoxia on metabolism.@*RESULTS@#(1) OPLS-DA analysis showed that R2Y was 0.967 and Q2 was 0.796, indicating that the model was reliable. (2) Volcano plot and heat map analysis showed significant statistical differences in the expression levels of metabolites between the two groups, with 541 up-regulated metabolites, 64 down-regulated metabolites, and 907 no differences, while the elevated 5-hydroxy-L-lysine was the most significant differential metabolite induced by high oxygen. (3) KEGG pathway enrichment analysis showed that porphyrin and chlorophyll metabolism (P = 0.005), lysine degradation (P = 0.047), and aromatic compound degradation (P = 0.024) were the targets affected by hyperoxia. (4) Differential analysis of metabolic products through KEGG enrichment pathway showed that hyperoxia had a significant impact on the metabolism of porphyrin and chlorophyll, lysine, and aromatic compounds such as benzene and o-cresol.@*CONCLUSIONS@#Hyperoxia significantly induces intestinal metabolic disorders. Hyperoxia enhances the metabolism of porphyrins and chlorophyll, inhibits the degradation of lysine, and delays the degradation of aromatic compounds such as benzene and o-cresol.