[Effect of Low-Dose Recombinant Interleukin-2 Therapy on Immunocyte Subsets in Children with Solid Tumor].

OBJECTIVE: To evaluate the effect of low-dose recombinant interleukin-2 (rIL-2) therapy on immunocyte subsets and its side effects in children with solid tumor. METHODS: A total of 22 children (11 males and 11 females) with solid tumor in our department from December 2012 to November 2017 were selected, with a median age of 9 (3-16) years old when starting IL-2 therapy. ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy, and 17 cases achieved complete remission (CR) and 5 cases achieved partial remission (PR). A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year: 4×105 IU/(m2·d), s.c. for every other day, 3 times per week. The immunocyte subsets were detected every 3 months until the end of treatment, meanwhile, disease condition and therapy-related side effects were followed up. RESULTS: After low-dose rIL-2 therapy in 22 children, the absolute values of CD3+ T cells, CD3-CD56+ natural killer cells, CD3+CD4+ helper T cells (Th) and CD3+CD8+ cytotoxic T cells were up-regulated remarkably, as well as Th/suppressor T cells (all P < 0.05). While, there were no significant differences in absolute value and proportion of CD4+CD25+CD127- Treg cells during therapy. Among the 17 children who achieved CR before rIL-2 therapy, 14 cases continued to maintain CR after therapy, while 3 cases relapsed, and with 2 died after treatment abandonment. The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment. In the early stage of low-dose rIL-2 therapy, 1 child developed skin rashes at the injection sites, and 2 children ran a slight to mild transient fever. Their symptoms disappeared without any organ damage after symptomatic treatment. CONCLUSION: Low-dose rIL-2 therapy has good drug tolerance, and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.

Temporal Trends of Asthma Among Children in the Western Pacific Region From 1990 to 2045: Longitudinal Observational Study.

BACKGROUND: Asthma has become one of the most common chronic conditions worldwide, especially among children. Recent findings show that the prevalence of childhood asthma has increased by 12.6% over the past 30 years, with >262 million people currently affected globally. The reasons for the growing asthma epidemic remain complex and multifactorial. OBJECTIVE: This study aims to provide an up-to-date analysis of the changing global and regional asthma prevalence, mortality, disability, and risk factors among children aged <20 years by leveraging the latest data from the Global Burden of Disease Study 2019. Findings from this study can help inform priority areas for intervention to alleviate the rising burden of childhood asthma globally. METHODS: The study used data from the Global Burden of Disease Study 2019, concentrating on children aged 0 to 14 years with asthma. We conducted an in-depth analysis of asthma, including its age-standardized prevalence, incidence, mortality, and disability-adjusted life years (DALYs), across diverse demographics, such as region, age, sex, and sociodemographic index, spanning 1990 to 2019. We also projected the future burden of the disease. RESULTS: Overall, in the Western Pacific Region, the age-standardized prevalence rate of asthma among children increased slightly, from 3898.4 cases per 100,000 people in 1990 to 3924 per 100,000 in 2019. The age-standardized incidence rate of asthma also increased slightly, from 979.2 to 994.9 per 100,000. In contrast, the age-standardized death rate of asthma decreased from 0.9 to 0.4 per 100,000 and the age-standardized DALY rate decreased from 234.9 to 189.7 per 100,000. At the country level, Japan experienced a considerable decrease in the age-standardized prevalence rate of asthma among children, from 6669.1 per 100,000 in 1990 to 5071.5 per 100,000 in 2019. Regarding DALYs, Japan exhibited a notable reduction, from 300.6 to 207.6 per 100,000. Malaysia also experienced a DALY rate reduction, from 188.4 to 163.3 per 100,000 between 1990 and 2019. We project that the burden of disease in countries other than Japan and the Philippines will remain relatively stable up to 2045. CONCLUSIONS: The study indicates an increase in the prevalence and incidence of pediatric asthma, coupled with a decrease in mortality and DALYs in the Western Pacific Region between 1990 and 2019. These intricate phenomena appear to result from a combination of lifestyle shifts, environmental influences, and barriers to health care access. The findings highlight that nations such as Japan have achieved notable success in managing asthma. Overall, the study identified areas of improvement in view of persistent disease burden, underscoring the need for comprehensive collaborative efforts to mitigate the impact of pediatric asthma throughout the region.

Effect of electroacupuncture on behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome. / ç”µé’ˆå¯¹æ ¢æ€§ç–²åŠ³ç»¼åˆå¾å¤§é¼ è¡Œä¸ºå­¦åŠæµ·é©¬ç‚Žæ€§å› å­çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the changes of behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome (CFS), so as to explore its possible mechanisms in the treatment of CFS. METHODS: Twenty-seven SD rats were randomly divided into control, model and electroacupuncture (EA) groups (n=9 rats in each group). The CFS model was established by multi-factor compound stress stimulation method. Rats of the EA group received EA (10 Hz) at "Shenting" (GV24) penetrating "Baihui" (GV20), "Dazhui" (GV14) for 15 min, twice a day for 14 days. The general conditions, Morris water maze test, open field test, the exhausted running platform were conducted for determining the rats' locomotor and learning-memory activities. H.E. staining was used to observe the morphological structure of neurons in hippocampal CA1 region. The contents of interleukin (IL)-10, IL-17 and transforming growth factor (TGF) ß1 in hippocampus and serum of rats were detected by ELISA, and the positive expressions of IL-10, IL-17 and TGF-ß1 in hippocampal CA1 region were detected by immunofluorescence staining. RESULTS: Compared with the control group, the score of general condition was increased (P<0.05), the escape latency was prolonged (P<0.05), the number of crossing the original platform was decreased (P<0.05), the numbers of crossing the grid and entering the central area were increased (P<0.05), and the exhaustive treadmill time was shortened (P<0.05) in the model group. The contents of IL-10 in the hippocampus and serum were decreased (P<0.05), while IL-17 and TGF-ß1 contents were increased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was decreased (P<0.05), while the intensity of IL-17 and TGF-ß1 were increased (P<0.05). After treatment, compared with the model group, the score of general condition was decreased (P<0.05), the escape latency was shortened (P<0.05), the number of crossing the original platform was increased (P<0.05), the numbers of crossing the grid and entering the central area were decreased (P<0.05), and the exhaustive treadmill time was prolonged (P<0.05) in the EA group. The contents of IL-10 in the hippocampus and serum were increased (P<0.05), while IL-17 and TGF-ß1 levels were decreased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was increased (P<0.05), while the intensity of IL-17 and TGF-ß1 were decreased (P<0.05). H.E. staining showed that in the model group, the number of neurons in the hippocampus decreased, with disordered arrangement and loose structure, and a small numbers of neuronal nuclei were missing. The degree of tissue damage of the EA group was milder than that of the model group. CONCLUSIONS: EA can alleviate fatigue and spatial learning and memory impairment in CFS rats, which may be related to the regulation of peripheral and central inflammation.

The induction of SHP-1 degradation by TAOK3 ensures the responsiveness of T cells to TCR stimulation.

Thousand-and-one-amino acid kinase 3 (TAOK3) is a serine and threonine kinase that belongs to the STE-20 family of kinases. Its absence reduces T cell receptor (TCR) signaling and increases the interaction of the tyrosine phosphatase SHP-1, a major negative regulator of proximal TCR signaling, with the kinase LCK, a component of the core TCR signaling complex. Here, we used mouse models and human cell lines to investigate the mechanism by which TAOK3 limits the interaction of SHP-1 with LCK. The loss of TAOK3 decreased the survival of naïve CD4+ T cells by dampening the transmission of tonic and ligand-dependent TCR signaling. In mouse T cells, Taok3 promoted the secretion of interleukin-2 (IL-2) in response to TCR activation in a manner that depended on Taok3 gene dosage and on Taok3 kinase activity. TCR desensitization in Taok3-/- T cells was caused by an increased abundance of Shp-1, and pharmacological inhibition of Shp-1 rescued the activation potential of these T cells. TAOK3 phosphorylated threonine-394 in the phosphatase domain of SHP-1, which promoted its ubiquitylation and proteasomal degradation. The loss of TAOK3 had no effect on the abundance of SHP-2, which lacks a residue corresponding to SHP-1 threonine-394. Modulation of SHP-1 abundance by TAOK3 thus serves as a rheostat for TCR signaling and determines the activation threshold of T lymphocytes.

Complete degradation of PET waste using a thermophilic microbe-enzyme system.

Enzymatic degradation has been proposed as a suitable solution for addressing PET pollution, but approximately 10 % of PET is left as nonbiodegradable. Microbes can completely degrade PET at the gram level per year. Based on the complementary benefits of microbes and enzymes, a microbe-enzyme system was created to completely degrade PET. Here, a thermophilic microbe-enzyme (TME) system composed of Bacillus thermoamylovorans JQ3 and leaf-branch compost cutinase variant (ICCG) was used to demonstrate the synergistic degradation of PET, enabling 100 % degradation of PET waste at a high PET loading level (360 g/L). Six endogenous PET hydrolases of strain JQ3 were discovered by employing an ester bond hydrolysis function-first genome mining (EGM) strategy and first successfully expressed in E. coli. These hydrolases could release TPA as the final product from PET and preferentially degraded BHET instead of MHET. Of these, carboxylesterase 39_5 and ICCG could degrade PET in a synergistic manner to generate 50 µM of TPA, which was greater than the sum of the individual treatments. Finally, the degradation pathway of the TME system was speculated to include biofilm formation, PET degradation and utilization. The successful implementation of this study rendered a scale-up degradation feasible of PET at a lower cost.

Hepatic palmitoyl-proteomes and acyl-protein thioesterase protein proximity networks link lipid modification and mitochondria.

Acyl-protein thioesterases 1 and 2 (APT1 and APT2) reverse S-acylation, a potential regulator of systemic glucose metabolism in mammals. Palmitoylation proteomics in liver-specific knockout mice shows that APT1 predominates over APT2, primarily depalmitoylating mitochondrial proteins, including proteins linked to glutamine metabolism. miniTurbo-facilitated determination of the protein-protein proximity network of APT1 and APT2 in HepG2 cells reveals APT proximity networks encompassing mitochondrial proteins including the major translocases Tomm20 and Timm44. APT1 also interacts with Slc1a5 (ASCT2), the only glutamine transporter known to localize to mitochondria. High-fat-diet-fed male mice with dual (but not single) hepatic deletion of APT1 and APT2 have insulin resistance, fasting hyperglycemia, increased glutamine-driven gluconeogenesis, and decreased liver mass. These data suggest that APT1 and APT2 regulation of hepatic glucose metabolism and insulin signaling is functionally redundant. Identification of substrates and protein-protein proximity networks for APT1 and APT2 establishes a framework for defining mechanisms underlying metabolic disease.

Telluribacter roseus sp. nov., Isolated from the Kumtag Desert Soil.

A pink-pigmented bacterium, designated as strain SYSU D00476T, was isolated from sandy soil collected from the Kumtag Desert in China. Colonies were opaque, smooth and of a slight convexity with a clearly defined border. Cells were rod-shaped, Gram-stain-negative, catalase- and oxidase-positive. Growth occurred at 4-45 ℃ (optimum at 28-30 ℃), pH 6.0-8.0 (optimum at 7.0), and with 0-3.0% NaCl (w/v, optimum at 0-2.0%). Major fatty acids (> 10%) were C16:0, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), iso-C17:0 3-OH and iso-C15:0. Polar lipids comprised of three unidentified polar aminolipids (ALs), two unidentified aminophosphoglycolipids (APLs), one unidentified glycolipid (GL) and three unidentified phospholipids (PLs). The predominant respiratory quinone was MK-7. The genomic DNA G + C content was 50.5%. The low digital DNA-DNA hybridization (dDDH, 27.4%) and average nucleotide identity (ANI, 85%) values between strain SYSU D00476T and Telluribacter humicola KCTC 42819T indicated that SYSU D00476T represent a distinct species. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SYSU D00476T belonged to the genus Telluribacter, showing 97.5% similarity with T. humicola KCTC 42819T. All these data support that strain SYSU D00476T represent a novel species of the genus Telluribacter within the family Spirosomataceae, named as Telluribacter roseus sp. nov. The type strain is SYSU D00476T (= KCTC 82285T = CGMCC 1.18647T = MCCC 1K04983T).

Rubellimicrobium arenae sp. nov., isolated from desert soil.

Two Gram-stain-negative strains, designated as SYSU D00286T and SYSU D00782, were isolated from a sand sample collected from the Kumtag Desert in Xinjiang, north-west China. Cells were aerobic, non-motile and positive for both oxidase and catalase. Growth occurred at 4-37 °C (optimum, 28-30 °C), pH 6.0-7.0 (optimum, pH 7.0) and NaCl concentration of 0-1.5 % (w/v; optimum, 0%). Growth was observed on Reasoner's 2A agar and nutrient agar, but not on Luria-Bertani agar and trypticase soy agar. The polar lipids were identified as diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, three unidentified aminolipids, one unidentified glycolipid and two unidentified phospholipids. The major respiratory quinone was ubiquinone-10 and the major fatty acids (>10 %) were C16 : 0 and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The 16S rRNA gene sequence similarity between strains SYSU D00286T and SYSU D00782 was 100%, and their average nucleotide identity (ANI), average amino acid identity and (AAI) digital DNA-DNA hybridization (dDDH) values were all 100.0 %. Phylogenetic analysis indicated that these two strains belong to the same species of the genus Rubellimicrobium and show the highest sequence similarity to Rubellimicrobium rubrum KCTC 72461T (98.2 %) and Rubellimicrobium roseum CCTCC AA 208029T (97.5 %). The ANI, AAI and dDDH values between SYSU D00286T (as well as SYSU D00782) and the other five Rubellimicrobium type strains were all less than or equal to 83.2, 80.1 and 23.6 %, respectively. Based on their phylogenetic, phenotypic and chemotaxonomical features, strains SYSU D00286T and SYSU D00782 represent a novel species of the genus Rubellimicrobium, for which the name Rubellimicrobium arenae sp. nov. is proposed. The type strain is SYSU D00286T (=MCCC 1K04981T=CGMCC 1.8626T=KCTC 82271T).

Research progress on central mechanism of acupuncture treatment for chronic fatigue syndrome.

Chronic fatigue syndrome is a neurological disorder characterized by extreme fatigue that lasts for a long time and doesn't alleviate with rest. The number of the cases has been increasing during the era of COVID-19 pandemic. Acupuncture may have some effect on chronic fatigue syndrome, but its mechanism remains unclear. This article was to summarize the specific manifestations of abnormal central mechanism in patients with chronic fatigue syndrome through laboratory tests and neuroimaging. It was found from the laboratory evaluation that there were changes in the structure of the frontal cortex, thalamus and other brain tissues; factors, including IFN-α and IL-10 in cerebrospinal fluid were found abnormal; results of oxidative and nitrosative stress and changes in neurobiochemical substances, e.g. hypothalamus hormone levels and neurotransmitter concentrations, were observed. With magnetic resonance imaging and positron emission tomography, it was shown that the partial brain of persons with chronic fatigue syndrome had morphological changes with diminished grey matter and white; changes in cerebral blood flow velocity caused by decreased perfusion and functional activity with abnormal connectivity in brain were detected. In addition, there was significant decrease in glucose metabolism accompanied with neuroinflammatory response; metabolic disorders of serotonergic, cholinergic, glutamatergic and γ-aminobutyric acid energy neurotransmitters were also discovered. The regulatory effect of acupuncture on the above central neurological abnormalities in chronic fatigue syndrome model animals was elaborated, and the direction for further research was analyzed in order to provide ideas for further research on the central mechanism of acupuncture treatment for chronic fatigue syndrome.

Palmitoylation couples insulin hypersecretion with ß cell failure in diabetes.

Hyperinsulinemia often precedes type 2 diabetes. Palmitoylation, implicated in exocytosis, is reversed by acyl-protein thioesterase 1 (APT1). APT1 biology was altered in pancreatic islets from humans with type 2 diabetes, and APT1 knockdown in nondiabetic islets caused insulin hypersecretion. APT1 knockout mice had islet autonomous increased glucose-stimulated insulin secretion that was associated with prolonged insulin granule fusion. Using palmitoylation proteomics, we identified Scamp1 as an APT1 substrate that localized to insulin secretory granules. Scamp1 knockdown caused insulin hypersecretion. Expression of a mutated Scamp1 incapable of being palmitoylated in APT1-deficient cells rescued insulin hypersecretion and nutrient-induced apoptosis. High-fat-fed islet-specific APT1-knockout mice and global APT1-deficient db/db mice showed increased ß cell failure. These findings suggest that APT1 is regulated in human islets and that APT1 deficiency causes insulin hypersecretion leading to ß cell failure, modeling the evolution of some forms of human type 2 diabetes.

Perinatal lethal Gaucher disease due to compound heterozygosity of the splicing mutations in GBA gene.

OBJECTIVE: In order to figure out the cause for two consecutive fetuses with nonimmune hydrops fetalis (NIHF) in a Taiwanese couple, whole-Exome Sequencing and Sanger Sequencing were applied for the family. CASE REPORT: The two fetuses developed NIHF at gestation age of 19 and 21 weeks, respectively. The clinical features included ascites and pleural effusion, flattened nasofrontal angle, skin edema, clenched hands, ambiguous genitalia, hepatosplenomegaly and fetal thrombocytopenia. Magnetic resonance imaging of the brain showed cerebellar hypoplasia and delayed cortical maturation. The GBA deleterious variants c.1505+5G > C and c.308-1G > A were both detected in the two fetuses. CONCLUSION: The report provided the precious experience of the clinical presentation of perinatal lethal Gaucher disease (PLGD) and advice on reproductive medicine for the next pregnancy in a couple. The novel genetic mutations identified in the study also contribute to the known spectrum of PLGD-related mutations.

Leech-Centipede Granules Suppress EndMT to Improve Erectile Dysfunction in Rats with Diabetes Mellitus via TGF-ß/Smad Pathway.

OBJECTIVE: To investigate whether Leech-Centipede (LC) Granules can improve erectile function in rats with diabetes mellitus-associated erectile dysfunction (DMED) through endothelial-to-mesenchymal transition (EndMT) inhibition. METHODS: Components of LC Granules were identified via ultra-high-performance liquid chromatography. Thirty male Sprague Dawley rats were injected with streptozotocin and fed continuously for 8 weeks to establish the DMED rat model. Rats with erectile dysfunction symptoms diagnosed using apomorphine were divided into DMED and low-, medium-, and high-doses LC groups (n=6 in each). The negative control (NC, n=6) and DMED groups were given 5 mL of deionized water via intragastric gavage, and the low-, medium- and the high-doses LC groups were administered LC at 1.6, 3.2, and 6.4 g/kg, respectively, via intragastric gavage for 4 weeks. The intracavernous pressure (ICP), mean arterial pressure (MAP), and nitric oxide (NO) levels in cavernous tissue were measured for each group. Quantitative reverse transcription-polymerase chain reaction and Western blot were used to detect mRNA and protein expressions of endothelial and mesenchymal markers. Immunofluorescence staining was used to observe α-SMA, and Masson's trichrome staining was performed to determine the myofiber/collagen ratio. RESULTS: A total of 474 active components were identified. After treatment, the ICP/MAP value and NO level were significantly higher in the medium- and high-dose LC groups than in the DMED group (P<0.05). Compared with the DMED groups, the medium- and high-dose groups LC significantly increased and decreased endothelial and mesenchymal markers expression, respectively (P<0.05). Tumor growth factor (TGF)ß R II, p-Smad2, and p-Smad3 levels were considerably higher following diabetes onset but reduced following LC intervention (P<0.05), except for TGF ß 1 (P>0.05). α-SMA expression was significantly higher in the DMED group and was reduced in all LC intervention groups (P>0.05). The myofiber/collagen ratio in the LC groups was higher than that in the DMED group but lower than that in the NC group (all P<0.05). CONCLUSIONS: LC Granules may improve the erectile function of DMED rats by suppressing TGF-ß/Smad pathway to reverse EndMT.

Prediction of Severe Esophageal Varices in Patients With Cirrhosis Based on Levitt's CO Breath Test: A Proof of Concept Study.

GOALS: This study investigated the feasibility of using erythrocyte (RBC) lifespan determined by Levitt's CO breath test (LCOBT) to predict esophageal varices needing treatment (VNT) in patients with cirrhosis. BACKGROUND: Esophageal varix bleeding is a common fatal complication of cirrhosis and portal hypertension. The gold standard for identifying VNT is esophagogastroduodenoscopy (EGD), an invasive procedure with low patient compliance. VNT screening based on Baveno VI criteria has mediocre specificity. STUDY: RBC lifespan was determined by LCOBT in 53 cirrhotic patients (13 without varices, 11 mild/moderate varices, and 29 severe varices). Correlation of varix severity with RBC lifespan and other variables was analyzed. Rates of shortened RBC lifespan and thrombocytopenia (Baveno VI criteria) were compared. RESULTS: RBC lifespan correlated inversely with severity of varices ( r =-0.793, P <0.001). Mean RBC lifespans were 129±31, 96±21, and 59±21 days for Nonvarix, Mild/Moderate, and Severe groups. Shortened RBC lifespan (<75 d) was observed in 79.3% (23/29) of patients with severe varices, a frequency similar or identical to thrombocytopenia rates [original Baveno VI criteria, 86.2% (25/29), P =0.487; expanded criteria, 79.3% (23/29), P >0.999]. Among 24 patients without severe varices, shortened RBC lifespan was observed in 1 patient whereas thrombocytopenia was detected in 13 and 8 patients based on the original ( P <0.001) and expanded criteria ( P =0.010), respectively. CONCLUSIONS: RBC lifespan correlates inversely with varix severity in patients with cirrhosis. LCOBT may enable specific screening for VNT.

Hsa_circ_0000670 promoted the progression of gastric cancer through the miR-515-5p/SIX1 molecular axis / 中华肿瘤杂志

Objective: To explore whether hsa_circ_0000670 promotes the progression of gastric cancer by regulating the miR-515-5p/SIX1 molecular axis. Methods: The gastric cancer and adjacent normal tissues of 35 gastric cancer patients admitted to Rugao Hospital Affiliated to Nantong University from 2014 to 2015 were collected. The expression levels of circ_0000670, miR-515-5p and Sine oculis homeobox 1 (SIX1) in gastric cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The correlations between circ_0000670 and miR-515-5p, miR-515-5p and SIX1, circ_0000670 and SIX1 were analyzed by the Pearson method. Patients were divided into low circ_0000670 expression group (17 cases) and high circ_0000670 expression group (18 cases) based on the median of circ_0000670 expression level, and Kaplan-Meier was used to analyze the 5-year survival of patients. Cell proliferation was assessed via clone formation assay. Cell cycle and apoptosis were detected by flow cytometry. Wound healing and Transwell assays were used to detect cell migration and invasion ability. The targeting relationship between miR-515-5p and circ_0000670 or SIX1 was confirmed by the dual luciferase reporter assay. Nude mice were injected into HGC-27 cells transfected with sh-NC or sh-circ_0000670, and the volume and weight of the transplanted tumor were measured, also, the levels of circ_0000670, miR-515-5p and SIX1 in the transplanted tumor tissue were detected. Results: The expression levels of circ_0000670 and SIX1 in gastric cancer tissues and cell lines were significantly increased (P<0.05), while the expression levels of miR-515-5p were significantly decreased (P<0.05). The survival rate of patients in the low circ_0000670 expression group (82.4%) was significantly higher than that in the high circ_0000670 expression group (28.7%, P=0.034). Circ_0000670 was negatively correlated with miR-515-5p (r=-0.846, P<0.001), and miR-515-5p was negatively correlated with SIX1 (r=-0.615, P<0.001), but circ_0000670 was positively correlated with SIX1 (r=0.814, P<0.001). Transfection of si-circ_0000670 or miR-515-5p mimic could significantly reduce the number of clone-forming cells, migration distance, migration and invasion cells (P<0.05), and increase the ratio of G(0)/G(1) phase cells, apoptosis rate and the protein level of E-cadherin (P<0.05), decreased the proportion of S-phase cells and the protein level of Vimentin (P<0.05). The dual luciferase report assay confirmed that circ_0000670 could target miR-515-5p, and miR-515-5p could bind to SIX1. Co-transfection of si-circ_0000670 and miR-515-5p inhibitor could significantly attenuate the effects of si-circ_0000670 on cell proliferation, migration, invasion, cell cycle and apoptosis (P<0.05). Co-transfection of miR-515-5p mimic and pcDNA-SIX1 could significantly reduce the effects of miR-515-5p mimic on cell proliferation, migration, invasion, cell cycle and apoptosis (P<0.05). Compared with the sh-NC group [volume=(596.20±125.46) mm(3) and weight=(538.00±114.39) g], the volume and weight of transplanted tumors in the sh-circ_0000670 group [volume=(299.20±47.58) mm 3 and weight=(289.80±48.73 g)] were significantly reduced (P<0.05), the expression levels of circ_0000670 and SIX1 were significantly reduced (P<0.05), and the expression level of miR-515-5p was significantly increased (P<0.05). Conclusion: Knockdown of circ_0000670 could inhibit cell proliferation, migration, invasion of gastric cancer cells, induce cell cycle arrest in G(0)/G(1) phase and promote cell apoptosis by regulating the miR-515-5p/SIX1 axis.

Neurovascular coupling and central nervous system diseases / 中国药理学通报

Neurovascular coupling is the function of regulating blood flow of the central nervous system at the level of neurovascular units. The central nervous system diseases related to neurovascular coupling mainly include cerebrovascular diseases such as chronic cerebral ischemia and neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease and Lewy body dementia. The main mechanism of neurovascular coupling dysfunction leading to the above diseases is cerebrovascular dysfunction or loss,which leads to serious damage to neuronal ischemia and affects its function. Therefore,this paper reviews the research status of neurovascular coupling and its related central nervous system diseases,in order to guide the follow-up research. The purpose of this paper is to provide a basis for the prevention,relief and treatment of central nervous system diseases related to neurovascular coupling through the mechanism of neurovascular coupling.

Ginsenoside Rgl inhibits neuronal ferroptosis caused by ischemic stroke through activating of Nrf2/xCT/GPX4 axis / 中国药理学通报

Aim To study the inhibitory effect of ginsenoside Rgl on neuronal ferroptosis after ischemic stroke and its mechanism. Methods A model of oxygen glucose deprivation/reoxygenation (OGD/R) was established in HT22 cells, and the effect of Rgl on the viability of HT22 cells after OGD/R injury was detected by CCK-8. The effect of Rgl on ferroptosis in HT22 cells after OGD/R injury was detected by the test of ferroptosis markers GSH/GSSG, SOD, MDA, and Fe

Self-efficacy and positive thinking as predictors of health-related quality of life in women with stress urinary incontinence.

BACKGROUND: Stress urinary incontinence (SUI), which causes involuntarily leakage of urine, has an impact on many women and may affect self-efficacy, which, in turn, can lead to poor health-related quality of life (QOL). This study aimed to explore the effects of sociodemographic and health information, symptom distress, self-efficacy, and positive thinking on the health-related QOL (general QOL and urinary incontinence-specific QOL) of women with SUI. METHODS: A cross-sectional study design was used. Women with SUI were recruited from the obstetrics and gynecology outpatient department and urodynamics examination room of a hospital by convenience sampling from August 2021 to March 2022. Participants were surveyed on the following questionnaires: Urogenital Distress Inventory, Geriatric Self-efficacy Index for Urinary Incontinence, Positive Thinking Scale, 12-Item Short-Form Health Survey (SF-12), and Incontinence Impact Questionnaire Short Form. RESULTS: Participants (N = 135) had a mean age of 53.76 years old. The mean SF-12 physical component summary score was 48.48 (physical QOL), and the mental component summary score was 46.56 (mental QOL). The urinary incontinence-specific QOL score was 16.01. Women with greater positive thinking and higher self-efficacy for urinary incontinence had better physical and mental QOL. Women with less symptom distress of urinary incontinence and higher self-efficacy for urinary incontinence had better urinary incontinence-specific QOL. CONCLUSION: The health-related QOL of women with SUI is affected by many factors, including positive thinking, self-efficacy, and symptom distress. Healthcare professionals can provide multifaceted programs to improve the health-related QOL of women with SUI.

Tissue distribution and integrated pharmacokinetic properties of major effective constituents of oral Gegen-Qinlian decoction in mice.

Gegen-Qinlian decoction (GQD) is a classic traditional Chinese medicine (TCM) formula. GQD is effective against colon or liver-related diseases including ulcerative colitis, non-alcoholic fatty liver, and type 2 diabetes. In this study, a liquid chromatography-tandem mass spectrometry method was developed, validated, and then applied to reveal the tissue distribution and integrated pharmacokinetic properties of major effective constituents of oral GQD in mice. The established method was quick, sensitive, and accurate enough to analyze GQD constituents in plasma and tissue homogenate samples quantitatively. According to their concentrations in the portal vein, systemic circulation, liver and colon samples of the mice after oral administration of GQD, the concentration-time curves of the constituents were respectively plotted. The results showed that daidzein, baicalin, and baicalein had relatively high exposure levels in the livers, while puerarin, berberine, epiberberine, coptisine, palmatine, jatrorrhizine, magnoflorine, glycyrrhizic acid, and glycyrrhetinic acid were enriched in the colons. Given that these constituents have significant biological activity, they could be regarded as the major effective constituents of GQD in treating colon or liver-related diseases, respectively. In addition, the integrated pharmacokinetic properties of GQD were studied. The GQD "integrated constituent" reached peak concentration at 4.0 h in the portal vein, the systemic circulation, the livers, and the colons, with half-lives of 1.5-4.1 h and mean retention time of 4.5-6.3 h, respectively. Furthermore, the concentration of the GQD "integrated constituent" in the colons was approximately 10 times higher than that in the livers, both of which were much higher than that in the systemic circulation, indicating its accumulation in these tissues, especially in the colons. In conclusion, the tissue distribution and integrated pharmacokinetic properties of oral GQD were revealed in the study. The results of the tissue distribution study would contribute to identifying the major target tissues and effective constituents of GQD, while the results of the integrated pharmacokinetic study would help to explain the pharmacokinetic properties of oral GQD as a whole.

Effect analysis of trajectory screw technique in fragility fracture of pelvic ring / 中国骨伤

OBJECTIVE@#To assess the clinical efficacy of minimally invasive technology with trajectory screw fixation for fragility fractures of pelvic(FFP).@*METHODS@#A retrospective case control study was performed to analyze the clinical data of 35 patients with FFP who were treated and followed up between January 2016 and December 2019. There were 12 males and 23 females, aged from 65 to 99 years with an average of(75.4±7.8) years old. There were 13 cases of type Ⅱb, 7 cases of type Ⅱc, 8 cases of type Ⅲa, 2 cases of type Ⅲb, 2 cases of type Ⅲc, 1 case of type Ⅳb, and 2 cases of type Ⅳc according to Rommens FFP comprehensive classification. All patients received the treatment of minimally invasive technology with trajectory screws fixation. According to the different methods of anterior pelvic ring fixation, FFP patients were divided into two groups:12 cases were fixed with the pedicle screw rod system in the anterior pelvic subcutaneous internal fixator (INFIX) group;23 cases were fixed with hollow screws of the pubic symphysis, superior ramus of pubis or acetabular anterior column in the screw group. The operation time, intraoperative blood loss, intraoperative fluoroscopy times, length of hospital stay, cost of internal fixation, pre- and post-operative visual analogue scale(VAS) were compared between the two groups. The fracture reduction quality was evaluated according to the Matta criteria, and the clinical function was evaluated by the Majeed functional scoring system respectively.@*RESULTS@#All patients were followed up for 12 to 39(16.5±5.4) months after surgery. There was no statistically significant difference in the operation time, intraoperative blood loss, intraoperative fluoroscopy time, and length of hospital stay between the two groups(P>0.05). As for the cost of internal fixation, the cost of internal fixation in the screw group [2 914 (2 914, 4 371) yuan] was significantly lower than that of the INFIX group [6 205 (6 205, 6 205) yuan] (P<0.05). No significant difference was observed in the incidence of postoperative complications between the two groups (P>0.05). There was no significant difference in VAS assessment at admission, 1 week, and 3 months after surgery between the two groups(P>0.05). However, the VAS assessment at 1 week and 3 months after surgery of the two groups were significantly better than those at admission(P<0.05). There was no significant difference in the quality of fracture reduction after the operation and the efficacy evaluation at the last follow-up between the two groups(P>0.05).@*CONCLUSION@#For the treatment of fragility fractures, minimally invasive technology with trajectory screw fixation can achieve good clinical efficacy. It has the advantages of being relatively minimally invasive, less bleeding, relieving the pain. It deserves clinical application.

Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia / 中国结合医学杂志

OBJECTIVE@#To explore the effect of Kuanxiong Aerosol (KXA) on isoproterenol (ISO)-induced myocardial injury in rat models.@*METHODS@#Totally 24 rats were radomly divided into control, ISO, KXA low-dose and high-dose groups according to the randomized block design method, and were administered by intragastric administration for 10 consecutive days, and on the 9th and 10th days, rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA. In addition, the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test. The influence of KXA on the expression of calcium-CaM-dependent protein kinase II (CaMK II)/extracellular regulated protein kinases (ERK) signaling pathway has also been tested.@*RESULTS@#KXA significantly reduced the ISO-induced increase in ST-segment, interventricular septal thickness, cardiac mass index and cardiac tissue pathological changes in rats. Moreover, the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine (NE) or potassium chloride (KCl) was increased after KXA treatment in an endothelium-independent manner, and was attenuated by preincubation with verapamil, but not with tetraethylammonium chloride, 4-aminopyridine, glibenclamide, or barium chloride. KXA pretreatment attenuated vasoconstriction induced by CaCl2 in Ca2+-free solutions containing K+ or NE. In addition, KXA pretreatment inhibited accumulation of Ca2+ in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK II and p-ERK levels.@*CONCLUSION@#KXA may inhibit influx and release of calcium and activate the CaMK II/ERK signaling pathway to produce vasodilatory effects, thereby improving myocardial injury.