Oxytocin Receptor in Cerebellar Purkinje Cells Does Not Engage in Autism-Related Behaviors.

The classical motor center cerebellum is one of the most consistent structures of abnormality in autism spectrum disorders (ASD), and neuropeptide oxytocin is increasingly explored as a potential pharmacotherapy for ASD. However, whether oxytocin targets the cerebellum for therapeutic effects remains unclear. Here, we report a localization of oxytocin receptor (OXTR) in Purkinje cells (PCs) of cerebellar lobule Crus I, which is functionally connected with ASD-implicated circuits. OXTR activation neither affects firing activities, intrinsic excitability, and synaptic transmission of normal PCs nor improves abnormal intrinsic excitability and synaptic transmission of PCs in maternal immune activation (MIA) mouse model of autism. Furthermore, blockage of OXTR in Crus I in wild-type mice does not induce autistic-like social, stereotypic, cognitive, and anxiety-like behaviors. These results suggest that oxytocin signaling in Crus I PCs seems to be uninvolved in ASD pathophysiology, and contribute to understanding of targets and mechanisms of oxytocin in ASD treatment.

High-dose amoxicillin-proton pump inhibitor dual therapy as first-line treatment for Helicobacter pylori infection in Northwest China: A prospective, randomised controlled trial.

AIMS: We aimed to assess the eradication efficacy and factors that influencing it of high-dose dual therapy (HDDT) in Gansu region, Northwest China. METHODS: A total of 216 treatment-naive patients with Helicobacter pylori infection were randomly assigned to two groups for the 14-day eradication treatment: the HDDT group (amoxicillin 750 mg q.i.d. and esomeprazole 40 mg t.i.d.) and the amoxicillin and clarithromycin-containing bismuth quadruple therapy group (ACBQT: esomeprazole 20 mg, bismuth potassium citrate 2 g, amoxicillin 1 g, and clarithromycin 500 mg; b.i.d.). The eradication rates, adverse effects and patient compliance of these two groups were compared. Eradication efficacy was determined by 13 C urea breath test (13 C UBT) 4-8 weeks after finishing treatment. Antibiotic resistance was determined by the Epsilometer testing (E-test) method. RESULTS: The eradication rates for the HDDT and ACBQT groups were 71.0% and 74.7% (P = .552) by per-protocol analysis, and 65.7% and 68.5% (P = .664) by intention-to-treat analysis. The overall adverse event rates in the HDDT and ACBQT groups were 2.0% and 43.4% (P < .001), respectively. The resistance rates to amoxicillin, clarithromycin, tetracycline, levofloxacin and metronidazole were 15.2%, 42.0%, 5.4%, 35.7% and 83.0%, respectively. Amoxicillin resistance and delta over baseline (DOB) of 13 C UBT ≥ 20 before treatment significantly reduced the eradication rate in 112 participants with H. pylori cultured. CONCLUSION: The HDDT as first-line treatment for H. pylori was unsatisfactory in Gansu. Amoxicillin resistance and DOB of 13 C UBT ≥ 20 before treatment were significantly correlated with H. pylori eradication failure.

The effect of Chaihu-shugan-san on cytotoxicity induction and PDGF gene expression in cervical cancer cell line HeLa in the presence of paclitaxel +cisplatin.

Chaihu-shugan-san, as a traditional Chinese herbal formula, is composed of seven different herbs. This medicine can treat cancer due to its antioxidant compounds. In this study, the effect of Chaihu-shugan-san was considered on cytotoxicity induction and PDGF gene expression in cervical cancer cell line HeLa at different concentrations and at different times, by the MTT method. Paclitaxel + cisplatin were used as a control in this study. The expression of the PDGF gene was quantitatively evaluated in treated cells by real-time PCR, and a generalized linear model was used to evaluate the effect of the medicine, and Duncan's multiple range tests were used to evaluate the data. The results of the MTT test showed that Chaihu-shugan-san had antitumor properties in different concentrations, but there was a significant difference between this medicine and paclitaxel +cisplatin. Also, examination of gene expression showed that this medicine reduced the expression of the PDGF gene in the HeLa cancer cell line (P ? 0.04). Therefore, Chaihu-shugan-san could be suggested as an effective factor in preventing the growth of cervical cancer cells and controlling angiogenic factors that play an important role in the metastasis of cancerous tumors.

Forsythoside A inhibits adhesion and migration of monocytes to type II alveolar epithelial cells in lipopolysaccharide-induced acute lung injury through upregulating miR-124.

Acute lung injury (ALI) is a severe disease for which effective drugs are still lacking at present. Forsythia suspensa is a traditional Chinese medicine commonly used to relieve respiratory symptoms in China, but its functional mechanisms remain unclear. Therefore, forsythoside A (FA), the active constituent of F. suspensa, was studied in the present study. Inflammation models of type II alveolar epithelial MLE-12 cells and BALB/c mice stimulated by lipopolysaccharide (LPS) were established to explore the effects of FA on ALI and the underlying mechanisms. We found that FA inhibited the production of monocyte chemoattractant protein-1 (MCP-1/CCL2) in LPS-stimulated MLE-12 cells in a dose-dependent manner. Moreover, FA decreased the adhesion and migration of monocytes to MLE-12 cells. Furthermore, miR-124 expression was upregulated after FA treatment. The luciferase report assay showed that miR-124 mimic reduced the activity of CCL2 in MLE-12 cells. However, the inhibitory effects of FA on CCL2 expression and monocyte adhesion and migration to MLE-12 cells were counteracted by treatment with a miR-124 inhibitor. Critically, FA ameliorated LPS-induced pathological damage, decreased the serum levels of tumor necrosis factor-α and interleukin-6, and inhibited CCL2 secretion and macrophage infiltration in lungs in ALI mice. Meanwhile, administration of miR-124 inhibitor attenuated the protective effects of FA. The present study suggests that FA attenuates LPS-induced adhesion and migration of monocytes to type II alveolar epithelial cells though upregulating miR-124, thereby inhibiting the expression of CCL2. These findings indicate that the potential application of FA is promising and that miR-124 mimics could also be used in the treatment of ALI.

Type 2 myocardial infarction among critically ill elderly patients in the Intensive Care Unit: the clinical features and in-hospital prognosis.

BACKGROUND: Type 2 myocardial infarction (T2MI) refers to myocardial ischemic necrosis as a result of myocardial oxygen supply/demand mismatch, which are common comorbidities of critically ill patients. The purpose of this study was to investigate the incidence rate and risks of T2MI in critically ill elderly patients and further elucidate in-hospital prognostic factors. METHODS: A total of 223 critically ill elderly patients admitted to our hospital from October 2016 to September 2018 were recruited. The clinical data and the in-hospital mortality rate were compared between the T2MI and non-T2MI groups. Multivariate linear regression analysis was used to identify independent factors related to T2MI. The clinical data and incidence of T2MI were also compared between patients who survived and those who died; multivariate regression analysis was used to identify independent risk factors for in-hospital death and survival analysis was conducted. RESULTS: In this study, the incidence of T2MI was 24.2% (54/223), and the mortality rate of critically ill elderly patients was 39.0% (87/223). Multivariate linear regression analysis showed that severe hypoxemia, arrhythmia, shock, and multiple organ dysfunction syndrome (MODS) were independent risk factors of T2MI. Compared to the survival patients, the use of mechanical ventilation, the incidence of T2MI, APACHE II score, troponin T, high-sensitivity C-reactive protein, and procalcitonin levels were significantly higher in patients who died, while the estimated glomerular filtration rate (eGFR) was significantly decreased (all P < 0.05). In-hospital mortality was significantly increased in patients with T2MI (59.3% vs. 32.5%, P < 0.001). After adjustment for relevant factors, the incidence of T2MI, mechanical ventilation required, and eGFR reduction were independent and significant predictors of in-hospital death. CONCLUSIONS: Critically, ill elderly patients have a high incidence of T2MI. In addition to severe hypoxia, shock, and arrhythmia, MODS is also associated with T2MI. At the same time, the risk of in-hospital death is increased in patients with type 2 MI.

Inhibition of autophagy induced by PTEN loss promotes intrinsic breast cancer resistance to trastuzumab therapy.

This study aims to explore the effects of the phosphatase and tension homolog (PTEN) expression level on autophagic status and on the resistance of breast cancer to trastuzumab treatment. PTEN and LC3I/II were knocked down with shRNA expression vectors, which were transfected into estrogen receptor (ER)-positive breast cancer cell lines. After trastuzumab treatment, the changes in the autophagy signal transduction pathways and autophagic proteins (LC3I/II, p62, LAMP, and cathepsin B) in these stably transfected cells were detected using western blot. The cells were also orthotopically implanted into nude mice to explore the influence of PTEN knockdown on tumor size, cell viability, and autophagic proteins after trastuzumab treatment. Similar determinations were performed using the LC3I/II overexpressed shPTEN breast cancer cells (LC3I/II-shPTEN). Downregulation of PTEN and autophagic proteins LC3-I and LC3-II was observed in resistant human breast cancer samples. Knockdown of PTEN and PTEN+ LC3I/II with shRNA in breast cancer cells resulted in increased resistance to trastuzumab. Consistently, trastuzumab treatment could not effectively reduce tumor size. Significant decreases in the levels of autophagic proteins LC3I/II, LAMP, p62, cathepsin B, and PI3K-Akt-mTOR and the signaling pathway protein Akt were found in PTEN knockdown cells, compared to the PTEN normal group, after trastuzumab administration, both in vitro and in vivo. However, these findings were reversed with the LC3I/II-shPTEN treatment. Therefore, the loss of PTEN may promote the development of primary resistance to trastuzumab in breast cancer via autophagy defects.

Anti-Interleukin-1 Beta/Tumor Necrosis Factor-Alpha IgY Antibodies Reduce Pathological Allergic Responses in Guinea Pigs with Allergic Rhinitis.

This study aims to determine whether the combined blockade of IL-1ß and TNF-α can alleviate the pathological allergic inflammatory reaction in the nasal mucosa and lung tissues in allergic rhinitis (AR) guinea pigs. Healthy guinea pigs treated with saline were used as the healthy controls. The AR guinea pigs were randomly divided into (1) the AR model group treated with intranasal saline; (2) the 0.1% nonspecific IgY treatment group; (3) the 0.1% anti-TNF-α IgY treatment group; (4) the 0.1% anti-IL-1ß IgY treatment group; (5) the 0.1% combined anti-IL-1ß and TNF-α IgY treatment group; and (6) the fluticasone propionate treatment group. The inflammatory cells were evaluated using Wright's staining. Histopathology was examined using hematoxylin-eosin staining. The results showed that the number of eosinophils was significantly decreased in the peripheral blood, nasal lavage fluid, and bronchoalveolar lavage fluid (P < 0.05), and eosinophil, neutrophil, and lymphocyte infiltration and edema were significantly reduced or absent in the nasal mucosa and lung tissues (P < 0.05) in the combined 0.1% anti-IL-1ß- and TNF-α IgY-treated guinea pigs. The data suggest that topical blockade of IL-1ß and TNF-α could reduce pathological allergic inflammation in the nasal mucosa and lung tissues in AR guinea pigs.

Clinical significance of peripheral blood DDR1 and CtBP gene methylation detection in patients with acute pancreatitis.

To investigate the clinical value of methylation levels of peripheral blood DDR1 and CtBP genes in evaluating the severity of acute pancreatitis (AP). Collect 90 blood samples from AP patients and healthy volunteers, and test methylation levels of SPINK1, STAT3, KIT, CFTR, DDR1, CtBP1, CtBP2 genes by bisulfite amplicon sequencing (BSAS). The gene methylation and clinical predictors of SAP early prediction were determined by univariate and multifactorial analysis, respectively. (1) The methylation level of CtBP1 gene and MCTSI score were independent predictors of SAP, with AUC values of 0.723 and 0.8895, respectively. (2) The methylation levels of DDR1, CtBP2, CFTR and SPINK1 genes were statistically significant in HC group vs AP group, HC group vs MAP group, and HC group vs SAP group. (3) The combined detection of CtBP1 gene methylation level and MCTSI score predicted the sensitivity, specificity, AUC, and 95%CI of SAP were 0.750, 0.957, 0.902, and 0.816-0.989, respectively. (1) The methylation level of CtBP1 gene in peripheral blood is an independent risk factor for predicting SAP and is a potentially good predictor of SAP, and the combined testing with the MCTSI score does not further significantly improve the early predictive value for SAP. (2) The methylation levels of DDR1, SPINK1, CtBP2, and CFTR genes were potential indicators for recognizing AP.

Protective Effect of Silibinin on Lipopolysaccharide-Induced Endotoxemia by Inhibiting Caspase-11-Dependent Cell Pyroptosis.

OBJECTIVE: To explore the protective effect and the underlying mechanism of silibinin (SIB), one of the active compounds from Silybum marianum (L.) Gaertn in endotoxemia. METHODS: Mouse peritoneal macrophage were isolated via intraperitoneally injection of BALB/c mice with thioglycolate medium. Cell viability was assessed using the cell counting kit-8, while cytotoxicity was determined through lactate dehydrogenase cytotoxicity assay. The protein expressions of interleukin (IL)-1 α, IL-1 ß, and IL-18 were determined by enzyme-linked immunosorbent assay. Intracellular lipopolysaccharide (LPS) levels were measured by employing both the limulus amoebocyte lysate assay and flow cytometry. Additionally, proximity ligation assay was employed for the LPS and caspase-11 interaction. Mice were divided into 4 groups: the control, LPS, high-dose-SIB (100 mg/kg), and low-dose-SIB (100 mg/kg) groups (n=8). Zebrafish were divided into 4 groups: the control, LPS, high-dose-SIB (200 εmol/L), and low-dose-SIB (100 εmol/L) groups (n=30 for survival experiment and n=10 for gene expression analysis). The expression of caspase-11, gasdermin D (GSDMD), and N-GSDMD was determined by Western blot and the expressions of caspy2, gsdmeb, and IL-1 ß were detected using quantitative real-time PCR. Histopathological observation was performed through hematoxylineosin staining, and protein levels in bronchoalveolar lavage fluid were quantified using the bicinchoninicacid protein assay. RESULTS: SIB noticeably decreased caspase-11 and GSDMD-mediated pyroptosis and suppressed the secretion of IL-1 α, IL-1 ß, and IL-18 induced by LPS (P<0.05). Moreover, SIB inhibited the translocation of LPS into the cytoplasm and the binding of caspase-11 and intracellular LPS (P<0.05). SIB also attenuated the expression of caspase-11 and N-terminal fragments of GSDMD, inhibited the relative cytokines, prolonged the survival time, and up-regulated the survival rate in the endotoxemia models (P<0.05). CONCLUSIONS: SIB can inhibit pyroptosis in the LPS-mediated endotoxemia model, at least in part, by inhibiting the caspase-11-mediated cleavage of GSDMD. Additionally, SIB inhibits the interaction of LPS and caspase-11 and inhibits the LPS-mediated up-regulation of caspase-11 expression, which relieves caspase-11-dependent cell pyroptosis and consequently attenuates LPS-mediated lethality.

[Influence of the depth of the sperm counting chamber on sperm motility].

OBJECTIVE: To investigate the influence of the depth of the sperm counting chamber on sperm motility. METHODS: We measured the depths of sperm counting chambers using the Filmetrics F20 Spectral Reflectance Thin-Film Measurement System. Then, according to the WHO5 manual, we analyzed 36 semen samples for the percentages of progressively motile sperm (PR) and non-progressively motile sperm (NP) and sperm motility (PR + NP) with the Ruiqi CFT-9201 computer-aided sperm analysis system, and compared the results of analysis. RESULTS: The depths of the 4 sperm counting chambers were 9.8, 12.7, 15.7 and 19.9 microm, respectively, and the obtained PR were (44.00 +/- 11.63), (41.96 +/- 12.62), (40.86 +/- 11.71) and (37.78 +/- 11.38)%, NP (13.54 +/- 3.01), (14.13 +/- 2.94), (14.91 +/- 3.02) and (16.53 +/- 2.77)%, and sperm motility (57.53 +/- 11.06), (56.08 +/- 11.97), (55.78 +/- 11.55) and (54.31 +/- 12.11)% from the 4 chambers, respectively. The depth of the sperm counting chamber was correlated negatively with PR (r = -0.993, P < 0.05) and sperm motility (r = -0.978, P < 0.05), but positively with NP (r = 0.989, P < 0.05). There were statistically significant differences between the 9.8 microm and 19.9 microm deep chambers in PR and NP (P < 0.05) though not in sperm motility among the 4 chambers of different depths. CONCLUSION: The impact of the depth of the sperm counting chamber on sperm motility should not be ignored, for the deviation of the results from the chambers of different depths may lead clinicians to incorrect diagnosis and consequently inappropriate therapeutic approaches. Different reference ranges of sperm motility need to be normalized in correspondence to the depths of sperm counting chambers.

Osteolytic Bone Loss and Skeletal Deformities in a Mouse Model for Early-Onset Paget's Disease of Bone with PFN1 Mutation Are Treatable by Alendronate.

A novel osteolytic disorder due to PFN1 mutation was discovered recently as early-onset Paget's disease of bone (PDB). Bone loss and pain in adult PDB patients have been treated using bisphosphonates. However, therapeutic strategies for this specific disorder have not been established. Here, we evaluated the efficiency of alendronate (ALN) on a mutant mouse line, recapitulating this disorder. Five-week-old conditional osteoclast-specific Pfn1-deficient mice (Pfn1-cKOOCL) and control littermates (33 females and 22 males) were injected with ALN (0.1 mg/kg) or vehicle twice weekly until 8 weeks of age. After euthanizing, bone histomorphometric parameters and skeletal deformities were analyzed using 3D µCT images and histological sections. Three weeks of ALN administration significantly improved bone mass at the distal femur, L3 vertebra, and nose in Pfn1-cKOOCL mice. Histologically increased osteoclasts with expanded distribution in the distal femur were normalized in these mice. Geometric bone shape analysis revealed a partial recovery from the distal femur deformity. A therapeutic dose of ALN from 5 to 8 weeks of age significantly improved systemic bone loss in Pfn1-cKOOCL mice and femoral bone deformity. Our study suggests that preventive treatment of bony deformity in early-onset PDB is feasible.

N-Butanol Extract of Glycyrrhizae Radix et Rhizoma Inhibits Dengue Virus through Targeting Envelope Protein.

BACKGROUND: At present, about half of the world's population is at risk of being infected with dengue virus (DENV). However, there are no specific drugs to prevent or treat DENV infection. Glycyrrhizae Radix et Rhizome, a well-known traditional Chinese medicine, performs multiple pharmacological activities, including exerting antiviral effects. The aim of this study was to investigate the anti-DENV effects of n-butanol extract from Glycyrrhizae Radix et Rhizome (GRE). METHODS: Compounds analysis of GRE was conducted via ultra-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). The antiviral activities of GRE were determined by the CCK-8 assay, plaque assay, qRT-PCR, Western blotting, and the immunofluorescence assay. The DENV-infected suckling mice model was constructed to explore the antiviral effects of GRE in vivo. RESULTS: Four components in GRE were analyzed by UHPLC-MS/MS, including glycyrrhizic acid, glycyrrhetnic acid, liquiritigenin, and isoliquiritigenin. GRE inhibited the attachment process of the virus replication cycle and reduced the expression of the E protein in cell models. In the in vivo study, GRE significantly relieved clinical symptoms and prolong survival duration. GRE also significantly decreased viremia, reduced the viral load in multiple organs, and inhibited the release of pro-inflammatory cytokines in DENV-infected suckling mice. CONCLUSIONS: GRE exhibited significant inhibitory activities in the adsorption stage of the DENV-2 replication cycle by targeting the envelope protein. Thus, GRE might be a promising candidate for the treatment of DENV infection.

Comparison of oral sodium phosphate tablets and polyethylene glycol lavage solution for colonoscopy preparation: a systematic review and meta-analysis of randomized clinical trials.

Objective: To systematically compare the bowel cleaning ability, patient tolerance and safety of oral sodium phosphate tablets (NaPTab) and oral polyethylene glycol electrolyte lavage solution (PEGL) to inform clinical decision making. Methods: PubMed, Embase, CBM, WanFang Data, CNKI, and VIP databases were searched for studies that used randomized controlled trials (RCTs) to compare the roles of NaPTab and PEGL in bowel preparation before colonoscopy. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias in the included papers. A meta-analysis was performed using RevMan 5.3 software. Results: A total of 13 RCTs were eligible for inclusion, including 2,773 patients (1,378 and 1,395 cases in the NaPTab and PEGL groups, respectively). Meta-analysis revealed no significant difference in the cleansing quality of the NaPTab and PEGL groups [RR 1.02, 95% CI (0.96-1.08), P = 0.46]. The incidence of nausea was lower in the NaPTab group than in the PEGL group [RR 0.67, 95% CI (0.58-0.76), p < 0.00001]. Patients rated the taste of NaPTab higher than PEGL [RR 1.33, 95% CI (1.26-1.40), P < 0.00001]. Willingness to repeat the treatment was also higher in the NaPTab group than in the PEGL group [RR 1.52, 95% CI (1.28-1.80), P < 0.00001]. Both serum potassium and serum calcium decreased in both groups after the preparation; however, meta-analysis revealed that both minerals decreased more in the NaPTab group than in the PEGL group [MD = 0.38, 95% CI (0.13-0.62), P = 0.006 for serum potassium and MD = 0.41, 95% CI (0.04-0.77), P = 0.03 for serum calcium]. Meanwhile, serum phosphorus increased in both groups after the preparation; however, levels increased more in the NaPTab group than in the PEGL group [MD 4.51, (95% CI 2.9-6.11), P < 0.00001]. Conclusions: While NaP tablets and PEGL were shown to have a similar cleaning effect before colonoscopy, NaP tablets had improved patient tolerance. However, NaP tablets had a strong effect on serum potassium, calcium, and phosphorus levels. For patients with low potassium, low calcium, and renal insufficiency, NaP tablets should be prescribed with caution. For those at high-risk for acute phosphate nephropathy, NaP tablets should be avoided. Given the low number and quality of included studies, these conclusions will require additional verification by large high-quality studies. Systematic review registration: 10.37766/inplasy2023.5.0013, identifier: NPLASY202350013.

Coinfection with influenza virus and non-typeable Haemophilus influenzae aggregates inflammatory lung injury and alters gut microbiota in COPD mice.

Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with high mortality rates. Viral and bacterial coinfection is the primary cause of AECOPD. How coinfection with these microbes influences host inflammatory response and the gut microbiota composition is not entirely understood. Methods: We developed a mouse model of AECOPD by cigarette smoke exposure and sequential infection with influenza H1N1 virus and non-typeable Haemophilus influenzae (NTHi). Viral and bacterial titer was determined using MDCK cells and chocolate agar plates, respectively. The levels of cytokines, adhesion molecules, and inflammatory cells in the lungs were measured using Bio-Plex and flow cytometry assays. Gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between cytokines and gut microbiota were determined using Spearman's rank correlation coefficient test. Results: Coinfection with H1N1 and NTHi resulted in more severe lung injury, higher mortality, declined lung function in COPD mice. H1N1 enhanced NTHi growth in the lungs, but NTHi had no effect on H1N1. In addition, coinfection increased the levels of cytokines and adhesion molecules, as well as immune cells including total and M1 macrophages, neutrophils, monocytes, NK cells, and CD4 + T cells. In contrast, alveolar macrophages were depleted. Furthermore, coinfection caused a decline in the diversity of gut bacteria. Muribaculaceae, Lactobacillus, Akkermansia, Lachnospiraceae, and Rikenella were further found to be negatively correlated with cytokine levels, whereas Bacteroides was positively correlated. Conclusion: Coinfection with H1N1 and NTHi causes a deterioration in COPD mice due to increased lung inflammation, which is correlated with dysbiosis of the gut microbiota.

WITHDRAWN: Design and Evaluation of Floating Micro-Carriers for Effective Delivery of a Hydrophobic Drug

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Effects of irrigation and nitrogen fertilization on mitigating salt-induced Na+ toxicity and sustaining sea rice growth.

This study investigated the effects of irrigation and nitrogen (N) fertilization on mitigating salt-induced Na+ toxicity and sustaining sea rice growth for perfecting irrigation and fertilization of sea rice. Three irrigation methods (submerged irrigation, intermittent irrigation, and controlled irrigation), three kinds of N fertilizers (urea, controlled release urea, and mixed N fertilizer), and control treatment without NaCl were set up in a pot experiment of sea rice with NaCl stress. The electrical conductivity in root layer soil of treatment with mixed N fertilizer and intermittent irrigation decreased slowly with the growth of rice and was significantly smaller than that of other treatments with NaCl. The Na+ content in sea rice of intermittent irrigation was the least, and that of submerged irrigation was significantly smaller than that of controlled irrigation, but the K+ and Ca2+ contents of three irrigation treatments were opposite to the Na+ content. The Na+ content of treatment with mixed N fertilizer and intermittent irrigation was the lowest, while the K+, Ca2+, and Mg2+ contents of mixed N fertilizer and intermittent irrigation were the highest in treatments with NaCl. The cell membrane permeability and malondialdehyde contents of rice leaves of mixed N fertilizer and intermittent irrigation were significantly smaller than those of other treatments with NaCl. The rice yield of mixed N fertilizer was significantly greater than that of urea and controlled release urea, and that of mixed N fertilizer and intermittent irrigation was increased by 104, 108, 277, 300, and 334% compared with mixed N fertilizer and submerged irrigation, urea and intermittent irrigation, urea and submerged irrigation, controlled release urea and intermittent irrigation, and controlled release urea and submerged irrigation, respectively. Therefore, the treatment of mixed N fertilizer and intermittent irrigation is worth recommending for being used for planting sea rice on coastal saline-sodic soil.

Anti-inflammatory, anti-angiogenetic and antiviral activities of dammarane-type triterpenoid saponins from the roots of Panax notoginseng.

Panax notoginseng has been used both as a traditional medicine and as a functional food for hundreds of years in Asia. However, the active constituents from P. notoginseng and their pharmacologic properties still need to be further explored. In this study, one new dammarane-type triterpenoid saponin (1), along with fourteen known analogs (2-15) were isolated and identified from the roots of P. notoginseng. The anti-inflammatory, anti-angiogenetic and anti-dengue virus effects of these isolated compounds were further evaluated. Compounds 1, 3, 5-7 and 10-12 exerted anti-inflammatory effects in two different zebrafish inflammatory models. Among them, 11, with the most significant activities, alleviated the inflammatory response by blocking the MyD88/NF-κB and STAT3 pathways. Moreover, compound 15 showed anti-angiogenetic activities in Tg(fli1:EGFP) and Tg(flk1:GFP) zebrafish, while 3 and 5 only inhibited angiogenesis in Tg(fli1:EGFP) zebrafish. Additionally, compounds 1, 3, 6, 8, 9 and 12 suppressed the replication of dengue virus either at the viral adsorption and entry stages or at the intracellular replication step. In conclusion, these findings enrich knowledge of the diversity of saponins in P. notoginseng and suggest that the dammarane-type triterpenoid saponins from P. notoginseng may be developed as potential functional foods to treat inflammation, angiogenesis or dengue-related diseases.

Clinicopathologic and Genomic Features in Triple-Negative Breast Cancer Between Special and No-Special Morphologic Pattern.

Background: Triple-negative breast cancer (TNBC) is refractory and heterogeneous, comprising various entities with divergent phenotype, biology, and clinical presentation. As an aggressive subtype, Chinese TNBC patients with special morphologic patterns (STs) were restricted to its incidence of 10-15% in total TNBC population. Methods: We recruited 89 patients with TNBC at Guangdong Provincial People's Hospital (GDPH) from October 2014 to May 2021, comprising 72 cases of invasive ductal carcinoma of no-special type (NSTs) and 17 cases of STs. The clinical data of these patients was collected and statistically analyzed. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples were collected for targeted next-generation sequencing (NGS) with cancer-related, 520- or 33-gene assay. Immunohistochemical analysis of FFPE tissue sections was performed using anti-programmed cell death-ligand 1(PD-L1) and anti-androgen receptor antibodies. Results: Cases with NSTs presented with higher histologic grade and Ki-67 index rate than ST patients (NSTs to STs: grade I/II/III 1.4%, 16.7%,81.9% vs 0%, 29.4%, 58.8%; p<0.05; Ki-67 ≥30%: 83.3% vs. 58.8%, p<0.05), while androgen receptor (AR) and PD-L1 positive (combined positive score≥10) rates were lower than of STs cases (AR: 11.1% vs. 47.1%; PD-L1: 9.6% vs. 33.3%, p<0.05). The most commonly altered genes were TP53 (88.7%), PIK3CA (26.8%), MYC (18.3%) in NSTs, and TP53 (68.8%), PIK3CA (50%), JAK3 (18.8%), KMT2C (18.8%) in STs respectively. Compared with NSTs, PIK3CA and TP53 mutation frequency showed difference in STs (47.1% vs 19.4%, p=0.039; 64.7% vs 87.5%, p=0.035). Conclusions: In TNBC patients with STs, decrease in histologic grade and ki-67 index, as well as increase in PD-L1 and AR expression were observed when compared to those with NSTs, suggesting that TNBC patients with STs may better benefit from immune checkpoint inhibitors and/or AR inhibitors. Additionally, lower TP53 and higher PIK3CA mutation rates were also found in STs patients, providing genetic evidence for deciphering at least partly potential mechanism of action.

Clinical analysis of the treatment of spinocerebellar ataxia and multiple system atrophy-cerebellar type with umbilical cord mesenchymal stromal cells.

BACKGROUND AIMS: The aims of this study were to observe the safety and effectiveness of umbilical cord mesenchymal stromal cells (UC-MSC) in the treatment of spinocerebellar ataxia (SCA) and multiple system atrophy-cerebellar type (MSA-C). METHODS: From October 2009 to September 2010, 14 cases of SCA and 10 cases of MSA-C were given UC-MSC by weekly intrathecal injection, at a dose of 1 × 10(6)/kg four times as one course. All the patients received one course of treatment, except three patients who received two courses. The movement ability and quality of daily life were evaluated with the International Cooperative Ataxia Rating Scale (ICARS) and Activity of Daily Living Scale (ADL) and the scores compared with those before cell therapy. A follow-up of 6-15 months was carried out for all of the patients. RESULTS: The results showed that the ICARS and ADL scores were significantly decreased 1 month after treatment (P < 0.01). The symptoms, including unstable walking and standing, slow movement, fine motor disorders of the upper limbs, writing difficulties and dysarthria, were greatly improved except for one patient, who had no response. The observed side-effects included dizziness (four patients), back pain (two cases) and headache (one case), which disappeared within 1-3 days. During the follow-up, 10 cases remained stable for half a year or longer, while 14 cases had regressed to the status prior to the treatment within 1-14 months (an average of 3 months). CONCLUSIONS: Intrathecal injection of UC-MSC is safe and can delay the progression of neurologic deficits for SCA and MSA-C patients.