Recent advances in small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase / 药学学报

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Clinical characteristics and prognosis of children with perianal fistulizing Crohn's disease / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical characteristics, treatment, and prognosis of children with perianal fistulizing Crohn's disease (pfCD).@*METHODS@#A retrospective analysis was conducted on the children, aged 6-17 years, who were diagnosed with Crohn's disease (CD) from April 2015 to April 2023. According to the presence or absence of perianal fistulizing lesions, they were divided into two groups: pfCD (n=60) and non-pfCD (n=82). The two groups were compared in terms of clinical characteristics, treatment, and prognosis.@*RESULTS@#The incidence of pfCD was 42.3% (60/142). The proportion of males in the pfCD group was higher than that in the non-pfCD group. Compared with the non-pfCD group, the pfCD group had a significantly higher proportion of children with involvement of the colon and small intestine or those with upper gastrointestinal lesions (P<0.05). Compared with the non-pfCD group, the pfCD group had a significantly higher rate of use of infliximab during both induction and maintenance treatment (P<0.05). In the pfCD group, the children with complex anal fistula accounted for 62% (37/60), among whom the children receiving non-cutting suspended line drainage accounted for 62% (23/37), which was significantly higher than the proportion among the children with simple anal fistula patients (4%, 1/23) (P<0.05). There were no significant differences between the two groups in mucosal healing rate and clinical remission rate at week 54 of treatment (P>0.05). The pfCD group achieved a fistula healing rate of 57% (34/60) at week 54, and the children with simple anal fistula had a significantly higher rate than those with complex anal fistula (P<0.05).@*CONCLUSIONS@#There is a high incidence rate of pfCD in children with CD, and among the children with pfCD, there is a high proportion of children with the use of biological agents. There is a high proportion of children receiving non-cutting suspended line drainage among the children with complex anal fistula. The occurrence of pfCD should be closely monitored during the follow-up in children with CD.

Responsibilities and influencing factors of infection control liaison nurses in general hospitals / 中国感染控制杂志

Objective To clarify the responsibilities and influencing factors of infection control liaison nurses(ICLNs)in general hospitals.Methods Relevant databases were systematically retrieved with scoping review method from establishment to March 18,2023,and the included literatures were reported standardizedly.Results A total of 36 literatures were included in the analysis.Responsibilities of ICLNs included admittance criteria,selec-tion methods,and job responsibilities.Influencing factors of ICLNs included training,empowerment,performance evaluation,continuous improvement measures,and personnel allocation.After the establishment of ICLNs,inci-dence of healthcare-associated infection and detection rate of multidrug-resistant organisms were reduced,compli-ance rate of health care workers'hand hygiene and monitoring rate of hospital environment were improved,and the cleaning and disinfection of hospital environment was standardized.Conclusion ICLNs play a role in preventing and controlling the occurrence of healthcare-associated infection.The management and application should be further standardized and improved,the effectiveness of ICLNs needs to be thoroughly studied,so as to promote the deve-lopment of ICLNs,and improve the quality of healthcare-associated infection management.

Alteration of brain functional connectivity strength in patients with type 2 diabetes and its neuropathological mechanism / 解放军医学杂志

Objective To explore the change of brain functional connectivity strength in patients with type 2 diabetes mellitus(T2DM)and its neuropathological mechanism.Methods Fifty-six T2DM patients who visited Gansu Provincial Hospital from October 2017 to March 2021 were selected as T2DM group,and 48 healthy controls were selected as control group.A prospective study was conducted on the changes in brain function in T2DM patients by analysis of resting state functional connectivity strength(FCS)and functional connectivity(FC)based on seed points.Brain functional magnetic resonance imaging,clinical variable collection,and neuropsychological testing of patients in two groups were performed.We calculate the FCS value,evaluate the brain function changes of the two groups in the resting state,take the brain regions with significant differences between the groups as the seed points and perform functional connectivity analysis with the whole brain.Correlation analysis was conducted between the FCS,FC values of the different brain regions and clinical variables such as fasting blood glucose(FPG),glycosylated hemoglobin(HbA1c),thyroid hormone(TSH)levels,as well as the scores of mini mental state examination(MMSE),Montreal cognitive assessment(MoCA),clock drawing test(CDT),Hamilton Depression Rating Scale(HAMD-24)and Hamilton Anxiety Scale(HAMA).Results Compared with control group,the HAMD-24 and HAMA scores in T2DM group significantly increased(P<0.01),while the MoCA scores decreased(P<0.05);In T2DM group,the FCS value of the right middle temporal gyrus increased(GRF correction,voxel level P<0.001,clustering level P<0.05),and the FC value of the right middle temporal gyrus-left anterior cingulate cortex decreased(GRF correction,voxel level P<0.001,clustering level P<0.05).Correlation analysis showed that the FC value of right middle temporal gyrus-left anterior cingulate cortex in T2DM patients was negatively correlated with HAMD-24 score(r=-0.395,P=0.003),HbA1c level(r=-0.303,P=0.023),and positively correlated with TSH level(r=0.324,P=0.017).Conclusions The increase of FCS value in the right middle temporal gyrus and the decrease of FC value in the right middle temporal gyrus-left anterior cingulate cortex may be important neuroimaging features of brain function damage in T2DM patients.HbA1c may play an important role in the process of brain damage in T2DM patients.

Patents research and development prospects of spleen-invigorating health food with the homology of medicine and food from 2000 to 2022: a bibliometric analysis / 数字中医药（英文）

@#,Objective To analyze the current status and development trends of the patents of spleen-invigorating health food with the homology of medicine and food in China, and to provide ideas and references for the research and development of traditional Chinese medicine (TCM) spleen-invigorating health food with the homology of medicine and food. @*Methods@#The State Administration for Market Regulation website’s “Special Food Information Query Platform” and the incoPat global patent database were searched in this study. Based on the methods of bibliometrics, the registered health food and patents related to spleen-invigorating health food with the homology of medicine and food in China were sorted out. Furthermore, the research and development numbers, provinces, institutions, technology and efficacy classification, major drugs, active ingredients and others of invigorating spleen health food in China were analyzed, and filtered patent data were visualized and analyzed by R programming language and CytoScape software. @*Results@# A total of 285 patents of health food with the homology of medicine and food for invigorating spleen were included and analyzed. From 2012, the patent registration numbers of these spleen-invigorating health food with the homology of medicine and food increased significantly in China. Over the past 20 years, the top five provinces in terms of patent disclosures were Guangdong, Anhui, Jiangsu, Shandong, and Guangxi. It was found that the technical efficacy of over 20 patents was described as “immune enhancement” “digestion” “disease prevention”, etc. Patent applications were mainly aimed at the research and development of the preservation of food or ingredients, the specific therapeutic activity of compounds, and pharmaceutical preparations, which were led by corporation research and development registrations, and supplemented by applications from research institutions and individuals. Among the 285 patents, the top 10 raw materials of spleen-invigorating health food with the homology of medicine and food were Shanyao (Dioscoreae Rhizoma), Fuling (Poria), Shanzha (Crataegi Fructus), Baizhu (Atractylodis Macrocephalae Rhizoma), Chenpi (Citri Reticulatae Pericarpium), Dazao (Jujubae Fructus), Gancao (Glycyrrhizae Radix et Rhizoma), Fengmi (Mel), Maiya (Hordei Fructus Germinatus), and Dangshen (Salviae Miltiorrhizae Radix et Rhizoma). The main functions were to nourish spleen and replenish Qi, invigorate spleen and benefit lungs, nourish blood and promote fluid production, and nourish spleen and stomach. @*Conclusion@#The main drug composition and functional components of spleen-invigorating health food with the homology of medicine and food are relatively clear, and the technical effects of invigorating the spleen and stomach, eliminating accumulation of food, and enhancing immunity are highly targeted. This paper provides evidence for the research and development, mechanism research, and process improvement of spleen-invigorating health food with the homology of medicine and food in the future.

Total flavonoids of Dracocephalum moldavica L. inhibit oxidative stress against H9c2 cell ischemia-reperfusion injury via VEGF-B/AMPK pathway / 药学学报

Total flavonoids of Dracocephalum moldavica L. (TFDM) is an effective component extracted and isolated from the traditional Uighur medicinal herb Cymbidium fragrans. Cymbidium fragrans has the effects of tonifying the heart and brain, promoting blood circulation and resolving blood stasis, and has been widely used in the treatment of cardiovascular and cerebrovascular diseases for a long time. The purpose of this study was to determine the effect of total flavonoids from Cymbidium fragrans on hypoxia/re-oxygenation (H/R) injury in H9c2 (rat cardiomyocytes) cells and its mechanism. A model (H/R) of hypoxia/re-oxygenation injury in H9c2 cells was established using hypoxia and glucose deprivation for 9 h combined with re-oxygenation and rehydration for 2 h to simulate myocardial ischemia-reperfusion injury. The effects of total flavonoids from Cymbidium fragrans on cell viability, markers of myocardial cell damage, oxidative stress levels, and reactive oxygen radical (ROS) content were investigated, Western blot was used to detect the expression of vascular endothelial growth factor B (VEGF-B) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway related proteins. The results showed that the total flavonoids of Cymbidium fragrans significantly increased the viability of myocardial cells after H/R injury, and decreased the content of lactate dehydrogenase (LDH) and creatine kinase isozyme (CK-MB) in the cell supernatant. It significantly reduced malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and decreased intracellular ROS and nitric oxide (NO) content. Western blot analysis showed that the total flavonoids of Cymbidium fragrans decreased Bax levels in H9c2 cells damaged by H/R and increased Bcl-2 expression. Total flavones of Cymbidium fragrans upregulate VEGF-B/AMPK pathway related proteins VEGF-B, vascular endothelial growth factor receptor 1 (VEGFR-1), neuropilin 1 (NRP-1), peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α), phosphorylated adenosine monophosphate activated protein (p-AMPK) and phospho mechanistic target of rapamycin (p-MTOR) levels. The above research results indicate that the total flavonoids of Cymbidium can significantly reduce the H/R injury of myocardial cells, which may be related to the upregulation of VEGF-B/AMPK pathway and inhibition of oxidative stress response.

Recent advances in small-molecule inhibitors targeting influenza virus glycoproteins / 药学学报

Hemagglutinin and neuraminidase, two important glycoproteins on the surface of influenza virus, play a considerable role in the entry and release stage of the viral life cycle, respectively. With in-depth investigation of influenza virus glycoproteins and the continuous innovation of drug discovery strategies, a new generation of glycoproteins inhibitors have been continuously discovered. From the point of view of medicinal chemistry, this review summarizes the current advances in seeking small-molecule inhibitors targeting influenza virus glycoproteins, hoping to provide valuable guidance for future development of novel antiviral drugs.

The technologies of small molecule ligand-target protein interaction and high throughput ligand screening / 药学学报

The interaction of drug and target protein is a critical part of new drug discovery. It is the premise for drugs to exert therapeutic effects by targeting specific binding sites of target proteins and thereby affecting its pharmacological activity. Currently, a variety of techniques are exploited to detect the interaction between drug ligands and target proteins. For example, cellular thermal shift assay (CETSA) and differential scanning fluorimetry (DSF) based on thermodynamics, mass spectrometry and nuclear magnetic resonance technology, etc. In addition, high-throughput ligand screening technology provides technical convenience for the search of specific ligand, and is a powerful tool to efficiently identify the interaction between drug ligand and target protein. Here, we summarize the detection techniques of interaction between small molecules and target proteins, and discuss the application of high-throughput ligand screening technology in drug research.

Label-free target identification for natural products based on proteomics / 药学学报

Target identification and verification of natural products is an important and challenging work in the field of chemical biology. It is also an important job for researchers to apply chemical proteomics technology to biomedicine in order to identify target proteins of natural products. Target identification is critical to understanding its mechanisms and developing natural products as molecular probes and potential therapeutic drugs. Traditional approaches of small molecule target identification based on affinity have been shown to be successful, such as click-chemical probes, radioisotope labeling or photosensitized small-molecule probes. Nevertheless, these technologies require purified candidate target proteins, and modified small molecules with probes or linkers, such as adding agarose beads, biotin labels, fluorescent labeling or photo-affinity labeling. Many structure-activity relationship studies should be performed to ensure that the addition of small molecule labels undisturbed the original biological activity of the small molecules. Unfortunately, all these modifications are likely to alter their biological activity or binding specificity. To overcome the bottleneck of "target recognition", researchers have developed a series of new techniques for unmodified drug target identification. In this article, we reviewed the target identification techniques of natural product without structural modification in order to provide reference for the development of natural products.

The neuroprotective effect of sodium pyruvate on mouse hippocampal neural HT22 cells / 中国药理学通报

Aim To study the effect of sodium pyruvate on apoptosis and autophagy of HT22 in mouse hippocampal neuronal cells under hypoxia conditions. Methods HT22 cells were incubated with different concentrations of sodium pyruvate to detect their cellular activity by MTS; iron staining was used to further observe the effect of sodium pyruvate on HT22 cells in mitochondrial metabolism; lysosomal staining was applied to detect the lysosomal changes of sodium pyruvate on HT22 cells; Western blot was used to detect the expression of Bcl-2, Bax and LC3-II/LC3- I proteins. Results To verify whether sodium pyruvate exerted neuroprotective effects on mouse hippocampal HT22 cells through affecting mitochondrial apoptosis and autophagy pathways, which were improved by administration of sodium pyruvate. Conclusions Sodium pyruvate administration under hypoxic conditions can reduce the neuroprotective effect of hypoxic injury by reducing apoptosis and activating autophagy in HT22 cells.

Expression profiles and regulatory network of microRNA, long non-coding RNA and circular RNA in rat chronic stress depression model based on whole transcriptome technology / 解剖学报

[Abstract] Objective To explore the potential pathophysiological mechanism of depression by screening the expression profiles and competing endogenous RNA (ceRNA) regulatory network microRNA(miRNA), long non-coding RNA(lncRNA) and circular RNA (circRNA) in the hippocampus of chronic stress depression rat model. Methods Twelve SD rats were divided into blank group and model group. Chronic mild unpredictability stress (CUMS) was used to construct the rat model of depression. The whole transcriptome analysis was performed on the hippocampus of the rats, and the possible regulatory networks among lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA were explored by bioinformatics method. Results According to the | fold change | ≥1. 5 and P≤0. 05, 29 differentially expressed miRNAs (21 up-regulated and 8 down-regulated), 686 differentially expressed lncRNAs (163 up-regulated and 523 down-regulated) and 8 differentially expressed circRNAs (3 up-regulated and 5 down-regulated) were identified. Gene Ontology (GO) and Kytot Encyclopedia of Genes and Genomes(KEGG) pathway analysis showed that the target genes of miRNAs were mainly enriched in the Golgi apparatus and calcium ion binding process in the cell membrane, the functions of lncRNAs target genes involved nucleic acid binding regulation, cytokine and protein ubiquitination, etc, and the functions of host genes of circRNAs were associated with cellular stimulation response, metabolic process, catalytic activity and other processes. The ceRNA network of lncRNAs and circRNAs showed complex interactions between non-coding RNA (ncRNA) and mRNA related to synaptic plasticity, such as protein Wnt-sa(WNT5a) and collagentype III alpha1(COL8a1) related to axon orientation and laminin A2(LAMA2) related to neurodevelopment. Conclusion The ceRNA network of lncRNA and circRNA shows that the complex interaction betweens ncRNA and mRNA is highly associated with the neuroplasticity, which support the neuroplasticity hypothesis of depression.

Correlation between chronic periodontitis and pulmonary ventilation function / 中国基层医药

Objective:To investigate the correlation between chronic periodontitis and pulmonary ventilation function.Methods:A total of 135 patients with chronic periodontitis who received treatment in Yuyao People's Hospital of Zhejiang Province between June 2014 and December 2019 were included in this study. They were divided into group A (stage I, initial lesion, n = 45), group B (stage II, early lesion, n = 45), group C (stage III, confirmed lesion, n = 45) according to the severity of periodontal lesion. Lung ventilation function indexes and serum levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha (TNF-α) were compared among the three groups. The correlation between periodontal condition and lung ventilation function indexes was analyzed. Results:Probing depth (PD), clinical attachment loss (CAL), number of missing teeth, alveolar bone resorption level were (1.67 ± 0.65) mm, (2.48 ± 0.44) mm, 0 pieces, and (1.38 ± 0.23) mm in group A, (2.05 ± 0.30) mm, (4.04 ± 0.97) mm, 1 piece, (3.37± 0.73) mm in group B, and (2.23 ± 0.47) mm, (5.17 ± 0.75) mm, 3 pieces, (6.48 ± 0.62) mm in group C. With the worsening of the disease, PD, CAL, number of missing teeth, and alveolar bone resorption level were gradually increased. PD, CAL and alveolar bone resorption level in group C were significantly higher than those in group A ( t = 4.68, 20.75, 51.74, all P < 0.001) and group B ( t = 2.17, 6.18, 21.78, P = 0.033, < 0.001, < 0.001). PD, CAL and alveolar bone resorption level in group B were significantly higher than those in group A ( t = 3.56, 9.82, 17.44, all P < 0.001). There was no significant difference in the number of missing teeth ( P > 0.05). Serum IL-6, IL-8 and TNF-α levels were (11.28 ± 4.26) ng/L, (7.48 ± 1.97) ng/L, (14.59 ± 2.11) ng/L in group A, (17.09 ± 4.91) ng/L, (10.82 ± 2.10) ng/L, (19.95 ± 4.48) ng/L in group B, and (26.47 ± 5.86) ng/L, (15.06 ± 2.75) ng/L, (33.76 ± 6.30) ng/L] in group C. With the worsening of the disease, serum IL-6, IL-8 and TNF-α levels were gradually increased. Serum IL-6, IL-8 and TNF-α levels in group C were significantly higher than those in group A ( t = 14.06, 15.03, 19.36, P < 0.001) and group B ( t = 8.23, 8.22, 11.98, all P < 0.001). Serum IL-6, IL-8 and TNF-α levels in group B were significantly higher than those in group A ( t = 6.00, 7.78, 7.26, P < 0.001). The percentage of the maximum expiratory volume in the first second to the predicted value (FEV 1%pre) and the ratio of the maximum expiratory volume in the first second to the forced vital capacity (FEV 1/FVC) were (81.53 ± 6.30)% and (68.73 ± 4.65)% in group A, (70.47 ± 5.25)% and (60.86 ± 3.42)% in group B, and (59.02 ± 3.41)% and (56.93 ± 4.21)% in group C. With the worsening of the disease, FEV 1%pre and FEV 1/FVC were gradually decreased. FEV 1%pre and FEV 1/FVC in group C were significantly lower than those in group A ( t = 21.08, 12.62, both P < 0.001) and group B ( t = 12.27, 4.86, both P < 0.001). FEV 1%pre and FEV 1/FVC in group B were significantly lower than those in group A ( t = 9.05, 9.25, both P < 0.001). Spearman correlation analysis showed that serum IL-6, IL-8 and TNF-α levels were negatively correlated with FEV1%pre and FEV 1/FVC ( r = -0.50, -0.28, -0.42, -0.61, -0.34, -0.51, all P < 0.05). Conclusion:There is a correlation between chronic periodontitis and pulmonary ventilation function. Inflammatory mediators may be involved in chronic periodontitis as internal systemic factors.

Gene polymorphisms of cytochrome B-245 alpha chain (CYBA) and cholesteryl ester transfer protein (CETP) and susceptibility to generalized aggressive periodontitis / 北京大学学报(医学版)

OBJECTIVE@#To explore the correlation of cytochrome B-245 alpha chain (CYBA) rs4673 and cholesteryl ester transfer protein (CETP) rs12720922 polymorphisms with the susceptibility of gene-ralized aggressive periodontitis (GAgP).@*METHODS@#The study was a case-control trial. A total of 372 GAgP patients and 133 periodontally healthy controls were recruited. The CYBA rs4673 and CETP rs12720922 polymorphisms were detected by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Logistic regression models were used to analyze the correlation of CYBA rs4673 and CETP rs12720922 variants with the susceptibility of GAgP. The interaction between the two gene polymorphisms to the susceptibility of GAgP was analyzed by the likelihood ratio test. The interaction model adopted was the multiplication model.@*RESULTS@#The mean age of GAgP group and control group was (27.5±5.2) years and (28.8±7.1) years respectively. There was significant difference in age between the two groups (P < 0.05). The gender distribution (male/female) was 152/220 and 53/80 respectively, and there was no significant difference between GAgP group and controls (P>0.05). For CYBA rs4673, the frequency of CT/TT genotype in the GAgP group was significantly higher than that in the controls [18.0% (66/366) vs. 10.6% (14/132), P < 0.05]. After adjusting age and gender, the individuals with CT/TT genotype had a higher risk of GAgP (OR=1.86, 95%CI: 1.01-3.45, P < 0.05), compared with CC genotype. There was no statistically significant difference in distributions of the CETP rs12720922 genotypes (GG, AA/AG) between GAgP patients and healthy controls (P>0.05). A significant interaction between CYBA rs4673 and CETP rs12720922 in the susceptibility to GAgP was observed. The GAgP risk of the individuals with CYBA rs4673 CT/TT and CETP rs12720922 GG genotypes was significantly increased (OR=3.25, 95%CI: 1.36-7.75, P < 0.01), compared with those carrying CC and AA/AG genotypes.@*CONCLUSION@#CYBA rs4673 CT/TT genotype is associated with GAgP susceptibility. There is a significant interaction between CYBA rs4673 CT/TT genotype and CETP rs12720922 GG genotype in the susceptibility of GAgP.

Effect of effective parts of Dracocephalum moldavica on the necroptosis of HBMECs after OGD/R injury / 药学学报

We investigated the ability of Dracocephalum moldavica (EPDM) flavonoids to protect human brain microvascular endothelial cells (HBMECs) from necroptosis induced by ischemia-reperfusion injury. To mimic the process of cerebral ischemia-reperfusion injury, a necroptosis model was established by treatment with the pan-cysteine aspartic acid protease (caspase) inhibitor Z-VAD-FMK combined with oxygen-glucose deprivation/re-oxygenation (OGD/R) injury using HBMECs. Cell proliferation and cytotoxicity (cell counting kit-8, CCK-8) was used to measure cell viability. A Hoechst33342/PI fluorescent double-staining method was exploited to determine the rate of cell necroptosis. A commercial kit was used to detect lactate dehydrogenase in the cell culture supernate. DCFH-DA probes, calcein AM and JC-1 probes were used to measure changes in ROS production, mitochondrial membrane permeability transformation pore (MPTP) opening and mitochondrial membrane potential (MMP), respectively. Enzyme-linked immunosorbent assay (ELISA) kits were chosen to detect the release of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Western blotting was used to detect necroptosis-related proteins. The results show that relative to control group, Z-VAD-FMK combined with OGD/R injury reduced cell viability, increased the necroptosis rate and the levels of LDH and ROS in HBMECs. The MPTP of the model group cells opened and the MMP reduced. TNF-α, IL-1β, and IL-6 levels were significantly elevated. Furthermore, the expression of receptor-interacting protein kinase 3 (RIP3) and mitochondrial phosphoglycerate mutase 5 (PGAM5) was significantly increased, accompanied by an increase of phosphorylated mixed-lineage kinase domain-like protein (p-MLKL)/MLKL. EPDM partially reversed the changes of the above-mentioned factors in HBMECs induced by Z-VAD-FMK plus OGD/R injury. These results indicate that EPDM may protect HBMECs from cerebral ischemia-reperfusion injury by inhibiting the RIP3/MLKL/PGAM5 pathway and MPTP opening to maintain mitochondrial function, thereby providing a scientific basis for the use of EPDM in the treatment of cerebral ischemia-related diseases.

Effect of electroacupuncture on laparoscope postoperative shivering in patients undergoing general anesthesia / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on laparoscope postoperative shivering in patients undergoing general anesthesia and explore its effect mechanism.@*METHODS@#A total of 80 patients with elective laparoscopic resection of intestinal tumor under general anesthesia were randomly divided into an EA group and a tramadol group, 40 cases in each group. Thirty min prior to the end of the operation, in the EA group, EA was exerted at Neimadian and Zusanli (ST 36), with disperse-dense wave, 2 Hz/100 Hz in frequency, 1 mA in intensity, and lasting 30 min. In the tramadol group, tramadol hydrochloride injection was dropped intravenously, 1 mg/kg. The conditions of shivering, dizziness, nausea, vomiting and agitation were observed in the post-anesthesia care unit (PACU). Heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were observed before treatment (T0), at the moment of extubation (T1), in 3 min of extubation (T2) and 1 h after operation (T3). Using ELISA, at T0 and T3, the expression levels of interleukin 6 (IL-6) and 5-hydroxytryptamine (5-HT) in plasma were detected separately. Choking and agitation were recorded during extubation.@*RESULTS@#① In the EA group, the incidence of shivering, dizziness, nausea, vomiting and agitation in the PACU was lower than that in the tramadol group (P<0.05). ②Compared with T0, HR, SBP and DBP were increased at T1 and T2 in the tramadol group (P<0.05). HR, SBP and DBP in the EA group were lower than the tramadol group at T1 and T2 (P<0.05). ③Compared with T0, the expression levels of IL-6 and 5-HT in plasma were increased at T3 in the tramadol group (P<0.05). The expression levels of IL-6 and 5-HT in the EA group were lower than the tramadol group at T3 (P<0.05). ④The incidence of choking and agitation during exudation in the EA group was lower than that in the tramadol group (P<0.05).@*CONCLUSION@#Electroacupuncture can reduce the incidence of laparoscopic postoperative shivering under general anesthesia. The potential mechanism mays related to the modulation of the expression levels of IL-6 and 5-HT caused by surgical trauma.

Distribution of mosquito species and associated viruses in Hami City of Xinjiang Uygur Autonomous Region from 2019 to 2020 / 中国血吸虫病防治杂志

Objective To investigate the distribution of mosquito species and their associated viruses, and identify Culex pipiens subspecies in Hami City, Xinjiang Uygur Autonomous Region. Methods Mosquitoes were captured using mosquito trapping lamps method in Yizhou District, Yiwu County, and Balikun County of Hami City in mi-July, 2019 and 2020. The species and subspecies of all captured mosquitoes were characterized. In addition, the flavivirus, alphavirus, bunyavirus, Japanese encephalitis virus, Liaoning virus, Tahyna virus, tick-borne encephalitis virus and West Nile virus were detected using reverse-transcription PCR assay in captured mosquitoes. Results A total of 1 496 mosquitoes were captured from Yizhou District, Yiwu County, and Balikun County of Hami City, belonging to 3 genus and 3 species. Cx. pipiens was the dominant mosquito species (986 mosquitoes, 65.91%), followed by Aedes caspius (457 mosquitoes, 30.55%), while Culiseta alaskaensis had the lowest number (53 mosquitoes, 3.54%). All captured Cx. pipiens mosquitoes were identified as Cx. pipiens pipiens based on the terminalia of male mosquitoes. RT-PCR assay tested negative for flavivirus, alphavirus, bunyavirus, Japanese encephalitis virus, Liaoning virus, Tahyna virus, tick-borne encephalitis or West Nile virus in captured Cx. pipiens mosquitoes. Conclusions There were 3 species of mosquitoes in Hami City from 2019 to 2020, including Cx. pipiens, Ae. Caspius and C. alaskaensis, with Cx. pipiens as the dominant mosquito species, and all captured Cx. pipiens mosquitoes were Cx. pipiens pipiens; however, no arboviruses were detected.

Xuebijing Injection Regulates Mitochondrial N-formyl Peptides/NLRP3 Inflammatory Pathway to Treat Severe Acute Pancreatitis in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Xuebijing injection （XBJ） on sodium taurocholate （Na-Tc）-induced severe acute pancreatitis （SAP） in rats. MethodForty rats were randomly assigned into 5 groups： sham operation group， SAP model group， and low-， medium-， and high-dose （4， 8， 12 mL·kg·d-1， respectively） XBJ groups. SAP model was established by retrograde injection of Na-Tc （1 mL·kg-1） into the biliary and pancreatic ducts. XBJ was injected intraperitoneally 3 days before and 0.5 h after modeling. The ascitic fluid volume and the pancreas weight-to-body weight ratio were measured. The pathological changes of pancreatic tissue were observed via hematoxylin-eosin （HE） staining. The protein levels of formyl peptide receptor 1 （FPR1） and nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） in pancreatic tissue were detected by immunohistochemistry. Western blot was employed to determine the expression levels of NADH-ubiquinone oxidoreductase chains 1-6 （MT-ND1， MT-ND2， MT-ND3， MT-ND4， MT-ND5， and MT-ND6） in rat plasma. ResultCompared with sham operation group， the SAP model group showcased increased ascitic fluid volume and pancreas weight-to-body weight ratio （P<0.05）， serious lesions in pancreatic tissue， increased total pathological score （P<0.05）， and up-regulated protein levels of FPR1 and NLRP3 in pancreatic tissue （P<0.05）. The model group had lower MT-ND2 level （P<0.05） and higher MT-ND1， MT-ND3， and MT-ND6 levels in plasma （P<0.05） than the sham operation group， while MT-ND4 and MT-ND5 had no significant differences between the two groups. Compared with SAP model group， the XBJ treatment decreased ascitic fluid volume and pancreas weight-to-body weight ratio （P<0.01）， ameliorated pancreatic lesions， and down-regulated the protein levels of FPR1 and NLRP3 in pancreatic tissue （P<0.01）. The treatments， especially high-dose XBJ （P<0.01）， down-regulated the expression of MT-ND1 （P<0.01）， MT-ND3 （P<0.01）， MT-ND6 （P<0.01）， and MT-ND4 and did not change that of MT-ND5. ConclusionXBJ may antagonize partial mitochondrial N-formyl peptides and excessive inflammatory response mediated by FPR1/NLRP3 to treat SAP in rats.

Study of the protective effect of total flavonoids of Dracocephalum moldavica L.On doxorubicin induced injury in HUVECs based on VEGF-B/AMPKa pathway / 中国药理学通报

Aim To investigate the protective effect of TFDM on doxorubicin-induced endothelial cell injury and its mechanism.Methods Cell viability was detected by CCK-8 assay.Cell morphology was observed by microscope.The changes of LDH, SOD and mitochondrial membrane potential were detected by kit method.Cell migration was detected by Transwell assay; Endothelial dysfunction and VEGF-B/AMPKa pathway related protein expression were detected by Western blot.Results Compared with model group, TFDM significantly increased cell viability, improved the morphologic changes of HUVEC induced by DOX, decreased LDH leakage, increased SOD activity, increased mitochondrial membrane potential, promoted endothelial cell migration, and inhibited endothelial cell injury.The results of Western blot showed that com pared with control group TFDM increased the expression levels of non-receptor tyrosine kinase ( Src) and focal adhesion kinase (FAK) .increased the phosphorylation level of eNOS, and decreased the expression level of ET-1 protein, thereby inhibiting endothelial dysfunction.The protein expression levels of VEGF-B, NRP1 , VEGFR1 and the ratio of p-AMPKa/AMPKa significantly increased in the administration group.Conclusion TFDM may inhibit doxorubicin-induced endothelial cell injury by activating VEGF-B/AMPKa pathway.

The mechanism of tilianin against ischemia-reperfusion injury of H9c2 cells / 药学学报

Z-VAD-FMK was combined with hypoxia-reoxygenation (H/R) injury to establish a necroptosis model of H9c2 cells to mimic the pathological changes of myocardial ischemia reperfusion injury (MIRI) in vitro and to study the effect and mechanism of tilianin against myocardial ischemia-reperfusion injury. A cell counting kit-8 (CCK-8) was used to detect cell viability, and commercial kits were used to detect lactate dehydrogenase (LDH) and superoxide dismutase (SOD) in the cell culture supernatant. Hoechst 33342/PI immunofluorescence staining was used to detect cell death. DCFH-DA, BBcellProbeTMM61, and JC-1 probes were used to detect reactive oxygen species (ROS), mitochondrial permeability transition pore (mPTP), and mitochondrial membrane potential (MMP), respectively. An enzyme-linked immunosorbent assay (ELISA) method was used to detect the release of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). The results show that the cell viability, SOD activity, and MMP of the model group induced by H/R injury decreased, as compared with control group, but the necroptosis rate, LDH level, and ROS release increased significantly. Furthermore, mPTP of the model group cells opened, and TNF-α, IL-1β, and IL-6 levels were significantly higher. Molecular docking modeling showed that tilianin can bind to calmodulin-dependent protein kinase II (CaMKII), and Western blot results showed that compared with control group, the expression levels of p-CaMKII and phospho-mixed lineage kinase domain-like protein increased in the model group, and tilianin could decrease the expression level of these proteins. The above results indicate that tilianin can protect H9c2 cells by inhibiting the phosphorylation of CaMKⅡ at threonine 287, protecting mitochondrial function, and inhibiting the opening of mPTP to prevent necroptosis. This study has value for research on new methods to treat H/R injury.

Metabolism characteristics and pharmacological insights of flavonoids based on the intestinal bacteria / 药学学报

The gut microbiota takes part in many in vivo important physiological activities of host, such as the substance metabolism and energy exchange, etc. The interaction between the host and the intestinal microorganisms has attracted scholars' attention. Flavonoids are a group of polyphenol compounds widely found in natural plants, with the bioactive effect of regulation of glucose and lipid metabolism, anti-inflammation. However, their low bioavailability cause difficulty to clarify the effective substances and the mechanism of flavonoids. Apart from the metabolic effects of liver on flavonoids, recent studies have shown that the gut microbiota can interact with flavonoids. On the one hand, flavonoids can be metabolized by gut microbiota and subsequent metabolites can produce pharmacological activities different from the parent components. On the other hand, flavonoids and their metabolites can in turn regulate the composition and physiological activities of the intestinal flora, which seems to provide a new insight for the research on the effective substances of flavonoids. In this review, we introduced the metabolic characteristics of flavonoids under the actions of intestinal bacteria, and the regulation effects of flavonoids on gut microbiota was also summarized. Meanwhile, the therapeutic effect of flavonoids under the action of intestinal bacteria was discussed.