Objective:To understand the whole genome and genetic evolution characteristics of the first epidemic influenza A (H3N2) viruses in Wuxi from 2022-2023.Methods:Real time fluorescence quantitative RT-PCR method was used to perform typing on respiratory samples of influenza cases. Virus isolation was performed on samples with positive nucleic acid of subtype A H3N2 influenza virus detected. After cell culture, nucleic acid was extracted from strains with red blood cell agglutination test (HA) ≥ 1∶8, whole genome sequence was amplified, library was constructed, and computer sequencing was performed using MiSeq sequencer. Using NC_007366.1 as reference strain, the data were analyzed using CLC Genomics Workbench (Version 23) software. The phylogenetic tree was constructed using MEGA 7.0 software, and the N-glycosylation sites were predicted by NetNGlyc 1.0 Server software.Results:The nucleotide homology and amino acid homology among 35 strains of influenza A H3N2 virus from 2022 to 2023 were 96.4%-100% and 95.2%-100%, respectively. The 16 epidemic strains in 2022 belong to the 3C.2a1b.2a.1a evolutionary branch, while the 19 epidemic strains in 2023 belong to the 3C.2a1b.2a.2a.3a.1 evolutionary branch. There are 7 differences in the nucleotide sequence of the HA gene between the 2022 epidemic strain and the corresponding vaccine strain, sharing 15 mutation sites; There are 28 differences in the nucleotide sequence of the HA gene between the 2023 epidemic strain and the corresponding vaccine strain, sharing 17 mutation sites. The HA genes of 35 epidemic strains all lack N-glycosylation site 61: NSS, while in 2023, the HA genes of 19 epidemic strains added N-glycosylation site 110: NSS.Conclusions:The HA and NA genes of influenza A H3N2 virus in 2022 and 2023 belong to two evolutionary branches, respectively, and both show specific amino acid site changes compared to the corresponding vaccine strains. The antigen matching between the 2022 epidemic strain and the vaccine strain is relatively good, while there is a risk of low antigen matching between the 2023 epidemic strain and the vaccine strain.

Acute mitral regurgitation(MR)in the setting of myocardial infarction(MI)may be the result of papillary muscle rupture(PMR).The clinical presentation can be catastrophic,with refractory cardiogenic shock.This condition is associated with high morbidity and mortality.Transcatheter edge-to-edge repair(TEER)has become increasingly common in treating severe mitral regurgitation.This case details a successful TEER is feasible and safe in patients with acute MR following MI.TEER is an emerging treatment option in this clinical scenario that should be taken into consideration.

Ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was employed in this study to observe the effect of Huaihua Powder on the serum metabolites of mice with ulcerative colitis and reveal the mechanism of Huaihua Powder in the treatment of ulcerative colitis. The mouse model of ulcerative colitis was established by dextran sodium sulfate salt(DSS). The therapeutic effect of Huaihua Powder on ulcerative colitis was preliminarily evaluated based on the disease activity index(DAI), colon appearance, colon tissue morphology, and the content of inflammatory cytokines such as tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β). UHPLC-Q-TOF-MS was employed to profile the endogenous metabolites of serum samples in blank control group, model group, and low-, medium-, and high-dose Huaihua Powder groups. Multivariate analyses such as principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed for pattern recognition. Potential biomarkers were screened by Mass Profiler Professional(MPP) B.14.00 with the thresholds of fold change≥2 and P<0.05. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that Huaihua Powder significantly improved the general state and colon tissue morphology of mice with ulcerative colitis, reduced DAI, and lowered the levels of TNF-α, IL-6, and IL-1β in serum. A total of 38 potential biomarkers were predicted to be related to the regulatory effect of Huaihua Powder, which were mainly involved in glycerophospholipid metabolism, glycine, serine, and threonine metabolism, mutual transformation of glucuronic acid, and glutathione metabolism. This study employed metabolomics to analyze the mechanism of Huaihua Powder in the treatment of ulcerative colitis, laying a foundation for the further research.
Mice ; Animals ; Colitis, Ulcerative/metabolism* ; Powders ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Metabolomics ; Colon ; Disease Models, Animal ; Biomarkers ; Dextran Sulfate/therapeutic use*

Stroke is the second leading cause of death in the world, of which about 60 % - 80 % are ischemic stroke. Ischemic stroke will inevitably cause the damage of neurons in the core area. With the increase of ischemic time, other neurons in the ischemic penumbra will also die due to the loss of " signal connection", and further lead to body dysfunction. In view of the complexity of neuronal death mechanism after ischemic stroke, understanding the action principle of death mechanism can better save ischemic penumbra neurons. This review mainly expounds several main mechanisms and potential therapeutic targets of neuronal death after ischemic stroke, so as to provide basis and help for the improvement of action mechanism research and drug development.

Aim To explore the material basis of anti-tumor effect of Compound Muji Granules. Methods The anti-tumor pharmacodynamics of Compound Muji Granules in vitro was studied by microfluidic chip technology. The fingerprint of Compound Muji Granules was established by HPLC. The "Spectrum-Material-Effect" of Compound Muji Granules was analyzed by grey correlation analysis,partial least squares regression analysis and network pharmacology approach. Results Seven batches of Compound Muji Granules with different extraction methods were successfully established. The results of grey correlation analysis showed that there was a positive correlation between Compound Muji Granules and 7 of the 14 components with pharmacodynamic correlation coefficient >0.80. The contribution of anti liver tumor was peak number 48(luteolin)>6(gallic acid)>19(chlorogenic acid)>59(quercetin)>67(kaempferol)>65(naringin)>38(ellagic acid),in that order. Conclusions Through the establishment of "Spectrum-Material-Effect" research method,it is clear that the above seven active monomers may be the anti-tumor material basis of Compound Muji Granules.

Aim To observe cellular damage and astrocyte activation at different time points of cerebral ischemia and reperfusion. Methods The middle cerebral artery of male SpragueDawley rats was occluded for 90 min followed by different time points of reperfusion. Eighty-five SPF male SD rats were randomly divided into control group (Sham), IR3, 6, 12, 24 and IR48h (MCAO followed by 48 h of reperfusion) group. Cerebral ischemia and reperfusion injury was observed by HE staining, and the structure of astrocytes was estimated with transmission electron microscopy (TEM). GFAP expression was detected by immunofluorescence staining and Western blot. Results Cerebral ischemia following by different time points of reperfusion led to different degrees of cellular damage, which was the most serious at 24 h of reperfusion. TEM showed destruction of astrocytes structure, swollen organelles and broken mitochondrial ridge. After cerebral ischemia-reperfusion, the expression levels of GFAP were significant up-regulated in the ischemic penumbra cortex and the highest was at 48 h of reperfusion, indicating astrocytes were activated. In addition, the results showed the gradual decrease in GFAP expression in the infarct core. Conclusions After cerebral ischemia-reperfusion, cellular damage is aggravated, and astrocytes are gradually activated in the ischemic penumbra. With the extension of reperfusion time, the boundaries of infarct area and ischemic area are gradually clear, and scarring may occur.

Ischemic stroke is the second leading cause of human death and the third reason of disability. Meanwhile, the incidence is rising year after year worldwide. Ischemic stroke could cause ischemia-reperfusion injury after blood recanalization treat-ment, but the mechanism of ischemia-reperfusion injury is still not very clear, so it is necessary to build a preclinical model with specific characteristics. Up to now, animal experiments have been still complicated, and the culture of brain slices has some limitations. The cell model in vitro has become a simplified and valuable tool widely used by researchers. The paper systematically summarizes the common type of nerve cells, and further analyzes establishment methods and principle, relevant research progress on the in vitro model of ischemia-reperfusion, in order to provide reference for rationally selecting hypoxia and reoxygenation model for basic research on cerebral ischemia and reperfusion and drug screening.

OBJECTIVE: To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options. METHODS: The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed. RESULTS: A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4－18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs. 28.08%, χ²= 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS. CONCLUSION POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.
Child ; Electrolytes ; Female ; Humans ; Male ; Metoprolol ; Midodrine ; Orthostatic Intolerance/therapy* ; Postural Orthostatic Tachycardia Syndrome/diagnosis* ; Retrospective Studies ; Salts ; Sitting Position ; Syncope, Vasovagal/diagnosis* ; Tilt-Table Test

ObjectiveTo explore the mechanism underlying the intervention of Gegen Qinliantang （GQL） in vulnerable plaques in atherosclerosis （AS） of ApoE^-/- mice by regulating the polarization of macrophages. MethodTwelve normal C57BL/6CNC mice were used as the control group， and 60 ApoE^-/- mice of the same line were randomized into 5 groups： model group， low-dose， middle-dose， and high-dose GQL groups （GQL-D， GQL-Z， and GQL-G groups， respectively）， and atorvastatin group （western medicine group）. High-fat diet was used for modeling. The control group and the model group were given （ig） equal volume of sterile distilled water， and GQL-D， GQL-Z， GQL-G， and western medicine groups received （ig） corresponding concentration of drugs for 8 weeks. The levels of total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected with biochemical methods. The distribution of plaques in the aortic region was observed based on oil red O staining and hematoxylin-eosin （HE） staining. Serum levels of M1 pro-inflammatory factors tumor necrosis factor （TNF）-α and interleukin （IL）-6 and M2 anti-inflammatory factors IL-13 and transforming growth factor （TGF）-β were detected by enzyme-linked immunosorbent assay （ELISA）. Protein expression of macrophage mannose receptor CD206/arginase-1 （Arg-1） and CD206/inducible nitric oxide synthase （iNOS） was determined by double-labeling immunofluorescence， and mRNA expression of aortic Arg-1 and iNOS by real-time polymerase chain reaction （PCR）. ResultLevels of TG， TC， and LDL-C were significantly lower and HDL-C level was significantly higher in the GQL-Z， GQL-G， and western medicine groups than in the model group. As the concentration of GQL rose， the area with plaques gradually shrunk and the color became lighter. The staining areas of the GQL-G group and the western medicine group were the most scattered. The administration groups showed significant increase in the protein levels of Arg-1 and CD206， significant decrease in the protein level of iNOS， significant rise of Arg-1 mRNA level， and significant drop of iNOS mRNA level （P<0.05）. ConclusionGQL intervenes in the vulnerable plaques in AS by improving lipid metabolism， inhibiting macrophage M1 polarization， promoting macrophage M2 polarization， and further improving the inflammatory microenvironment.

ObjectiveTo explore the effect of Gegen Qinliantang （GQL） on vulnerable plaque of atherosclerosis based on the macrophage pyroptosis mediated by nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3）/cysteine-aspartic acid protease （Caspase）-1 pathway. MethodA total of 12 normal C57BL/6CNC mice were used as the control group， and 60 ApoE^-/- mice of the same line were randomized into 5 groups： model group， low-dose， medium-dose， and high-dose GQL groups （GQL-D， GQL-Z， GQL-G groups， respectively）， and western medicine group. The control group and model group were given （ig） equal volume sterile distilled， and GQL-D， GQL-Z， GQL-G and western medicine groups received （ig） corresponding concentration of drugs for 8 weeks. Aortic plaques were observed based on hematoxylin and eosin （HE） staining. Serum levels of interleukin （IL）-1β and IL-18 were detected by enzyme-linked immunosorbent assay （ELISA）， protein levels of macrophage mannose receptor （CD206）/apoptosis-associated speck-like protein containing a CARD （ASC） and CD206/NLRP3 by double-labeling immunofluorescence， and C-terminal gasdermin D （GSDMD）， N-terminal GSDMD， NLRP3， pro-cysteinyl aspartate specific proteinase 1 （pro-Caspase-1） and NF-κB p65 by Western blot. ResultCompared with the control group， model group demonstrated serious pathological changes， rise of the levels of serum IL-1β and IL-18 and tissue ASC， NLRP3， C-terminal GSDMD， N-terminal GSDMD， pro-Caspase-1， and NF-κB p65， and decrease of CD206 level （P<0.05）. As compared with model group， the administration groups showed alleviation of the lesions in aortic wall， decrease in levels of serum IL-1β and IL-18 and tissue ASC， NLRP3， C-terminal GSDMD， N-terminal GSDMD， pro-Caspase-1， and NF-κB p65， and rise of CD206 level， with significant difference between some groups （P<0.05）. ConclusionGegen Qinliantang alleviates vulnerable plaque of atherosclerosis by regulating NF-κB/NLRP3/Caspase-1 pathway and further relieving macrophage pyroptosis.