[Study on Down-regulation of Interleukin-1ß Secretion by Inhibiting ABCC1/MRP1 Transporter].

OBJECTIVE: To screen interleukin (IL)-1ß secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice. METHODS: THP-1 cell line was differentiated to obtain human THP-1-derived macrophages, and the primary macrophages were obtained from human peripheral blood. FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice. The macrophages in abdominal cavity and bone marrow of mice were cultivated. The cells were treated with ABCC1/MRP1, ABCG2/BCRP, ABCB1/P-gp, OATP1B1, and MATE transporter inhibitors, then stimulated by lipopolysaccharide and adenosine triphosphate. The secretion level of IL-1ß was detected by ELISA, Western blot, and immunofluorescence. RESULTS: After inhibiting ABCC1/MRP1 transporter, the secretion of IL-1ß decreased significantly, while inhibition of the other 4 transporters had no effect. In animal experiment, the level of IL-1ß secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group (P < 0.05). CONCLUSION: ABCC1/MRP1 transporter is a newly discovered IL-1ß secretion pathway, which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study.

BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

[Ginsenoside Re regulates mitochondrial biogenesis through Nrf2/HO-1/PGC-1α pathway to reduce hypoxia/reoxygenation injury in H9c2 cells].

This article explored the mechanism by which ginsenoside Re reduces hypoxia/reoxygenation(H/R) injury in H9c2 cells by regulating mitochondrial biogenesis through nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/peroxisome prolife-rator-activated receptor gamma coactivator-1α(PGC-1α) pathway. In this study, H9c2 cells were cultured in hypoxia for 4 hours and then reoxygenated for 2 hours to construct a cardiomyocyte H/R injury model. After ginsenoside Re pre-administration intervention, cell activity, superoxide dismutase(SOD) activity, malondialdehyde(MDA) content, intracellular reactive oxygen species(Cyto-ROS), and intramitochondrial reactive oxygen species(Mito-ROS) levels were detected to evaluate the protective effect of ginsenoside Re on H/R injury of H9c2 cells by resisting oxidative stress. Secondly, fluorescent probes were used to detect changes in mitochondrial membrane potential(ΔΨ_m) and mitochondrial membrane permeability open pore(mPTP), and immunofluorescence was used to detect the expression level of TOM20 to study the protective effect of ginsenoside Re on mitochondria. Western blot was further used to detect the protein expression levels of caspase-3, cleaved caspase-3, Cyto C, Nrf2, HO-1, and PGC-1α to explore the specific mechanism by which ginsenoside Re protected mitochondria against oxidative stress and reduced H/R injury. Compared with the model group, ginse-noside Re effectively reduced the H/R injury oxidative stress response of H9c2 cells, increased SOD activity, reduced MDA content, and decreased Cyto-ROS and Mito-ROS levels in cells. Ginsenoside Re showed a good protective effect on mitochondria by increasing ΔΨ_m, reducing mPTP, and increasing TOM20 expression. Further studies showed that ginsenoside Re promoted the expression of Nrf2, HO-1, and PGC-1α proteins, and reduced the activation of the apoptosis-related regulatory factor caspase-3 to cleaved caspase-3 and the expression of Cyto C protein. In summary, ginsenoside Re can significantly reduce I/R injury in H9c2 cells. The specific mechanism is related to the promotion of mitochondrial biogenesis through the Nrf2/HO-1/PGC-1α pathway, thereby increasing the number of mitochondria, improving mitochondrial function, enhancing the ability of cells to resist oxidative stress, and alleviating cell apoptosis.

[Tetrahydropalmatine inhibiting mitophagy through ULK1/FUNDC1 pathway to alleviate hypoxia/reoxygenation injury in H9c2 cells].

This study explored the specific mechanism by which tetrahydropalmatine(THP) inhibited mitophagy through the UNC-51-like kinase 1(ULK1)/FUN14 domain containing 1(FUNDC1) pathway to reduce hypoxia/reoxygenation(H/R) injury in H9c2 cells. This study used H9c2 cells as the research object to construct a cardiomyocyte H/R injury model. First, a cell viability detection kit was used to detect cell viability, and a micro-method was used to detect lactate dehydrogenase(LDH) leakage to evaluate the protective effect of THP on H/R injury of H9c2 cells. In order to evaluate the protective effect of THP on mitochondria, the chemical fluorescence method was used to detect intracellular reactive oxygen species, intramitochondrial reactive oxygen species, mitochondrial membrane potential, and autophagosomes, and the luciferin method was used to detect intracellular adenosine 5'-triphosphate(ATP) content. Western blot was further used to detect the ratio of microtubule-associated protein 1 light chain 3(LC3) membrane type(LC3-Ⅱ) and slurry type(LC3-Ⅰ) and activated cleaved caspase-3 expression level. In addition, ULK1 expression level and its phosphorylation degree at Ser555 site, as well as the FUNDC1 expression level and its phosphorylation degree of Ser17 site were detected to explore its specific mechanism. The results showed that THP effectively reduced mitochondrial damage in H9c2 cells after H/R. THP protected mitochondria by reducing the level of reactive oxygen species in cells and mitochondria, increasing mitochondrial membrane potential, thereby increasing cellular ATP production, enhancing cellular activity, reducing cellular LDH leakage, and finally alleviating H/R damage in H9c2 cells. Further studies have found that THP could reduce the production of autophagosomes, reduce the LC3-Ⅱ/LC3-Ⅰ ratio, and lower the expression of the apoptosis-related protein, namely cleaved caspase-3, indicating that THP could reduce apoptosis by inhibiting autophagy. In-depth studies have found that THP could inhibit the activation of the ULK1/FUNDC1 pathway of mitophagy and the occurrence of mitophagy by reducing the phosphorylation degree of ULK1 at Ser555 and FUNDC1 at Ser17. The application of ULK1 agonist BL-918 reversely verified the effect of THP on reducing the phosphorylation of ULK1 and FUNDC1. In summary, THP inhibited mitophagy through the ULK1/FUNDC1 pathway to reduce H/R injury in H9c2 cells.

Low interleukin-10 level indicates a good prognosis in Salmonella enterica serovar typhimurium-induced pediatric hemophagocytic lymphohistiocytosis: A case report.

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients. There is no consensus on how to treat S. typhimurium-triggered sHLH. CASE SUMMARY: A 9-year-old boy with intermittent fever for 3 d presented to our hospital with positive results for S. typhimurium, human rhinovirus, and Mycoplasma pneumoniae infections. At the time of admission to our institution, the patient's T helper 1/T helper 2 cytokine levels were 326 pg/mL for interleukin 6 (IL-6), 9.1 pg/mL for IL-10, and 246.7 pg/mL for interferon-gamma (IFN-γ), for which the ratio of IL-10 to IFN-γ was 0.04. In this study, the patient received meropenem, linezolid, and cefoperazone/sulbactam in combination with high-dose methylprednisolone therapy (10 mg/kg/d for 3 d) and antishock supportive treatment twice. After careful evaluation, this patient did not receive HLH chemotherapy and recovered well. CONCLUSION: S. Typhimurium infection-triggered sHLH patient had a ratio of IL-10 to IFN-γ ≤ 1.33, an IL-10 concentration ≤ 10.0 pg/mL, and/or an IFN-γ concentration ≤ 225 pg/mL at admission. Early antimicrobial and supportive treatment was sufficient, and the HLH-94/2004 protocol was not necessary under these conditions.

Model-based precision dosing and remedial dosing recommendations for delayed or missed doses of isoniazid in Chinese patients with tuberculosis.

AIMS: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients. METHODS: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. RESULTS: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally. CONCLUSION: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.

[Water-soluble Inorganic Ion Content of PM2.5 and Its Change Characteristics in Urban Area of Beijing in 2022].

To explore the content and variation characteristics of water-soluble ions of atmospheric fine particles (PM2.5) in a Beijing urban area and put forward the pollution prevention and control scheme, the water-soluble ions, gaseous precursors (SO2, NO2), and meteorological factors (temperature, RH) of PM2.5 in 2022 were analyzed and determined. The results showed that the water-soluble ions with the highest proportion in PM2.5 in the Beijing City urban area were NO3-, NH4+, and SO42-, accounting for 52.7% of PM2.5. The mass concentrations of PM2.5 and SNA were lower than the historical results, whereas the proportion of SNA, SOR, and NOR was higher than the historical results. This showed that the fine particulate matter pollution in Beijing has been significantly improved, but it still has strong secondary pollution characteristics. NO3-/SO42-(2.2) was higher than those of historical and nearby provinces and cities, reflecting the expanding influence of mobile sources. In terms of seasonal variation, PM2.5 showed the characteristic of high in autumn and low in summer. The proportion of NO3- was the highest in autumn, spring, and winter; the proportion of SO42- was the highest in summer; and the proportion of NH4+ changed little in each season. The seasonal variation rules of NOR and SOR were almost opposite, which reflected the difference in transformation factors between NOR and SOR. The main forms of SNA in the Beijing urban area were NH4NO3 and (NH4)2SO4. The neutralization degree of cations and anions was the highest in winter, the cation NH4+ was slightly insufficient in summer, and NH4+ was in excess in spring and autumn. The Beijing urban area was an ammonia-rich environment. In terms of pollution level, RH, particulate matter moisture, and water-soluble ions mass concentration all increased with the increase in pollution level, and SNA increased fastest, with its proportion in PM2.5 increasing first and then stabilizing, whereas the contribution rate of other water-soluble ions decreased gradually. In terms of spatial distribution, the mass concentration relationship of SNA at the central urban area and suburbs was NO3- > SO42- > NH4+, which reflected the pollution characteristics dominated by NO3-. The highest contribution rate of SNA to PM2.5 occurred in the eastern region, the central urban area, and the transmission point, indicating that the secondary reaction was relatively active in the central urban area and the eastern region, and the regional transport was also an important source of secondary ions.

Nrf-2 as a novel target in radiation induced lung injury.

Radiation-induced lung injury (RILI) is a common and fatal complication of chest radiotherapy. The underlying mechanisms include radiation-induced oxidative stress caused by damage to the deoxyribonucleic acid (DNA) and production of reactive oxygen species (ROS), resulting in apoptosis of lung and endothelial cells and recruitment of inflammatory cells and myofibroblasts expressing NADPH oxidase to the site of injury, which in turn contribute to oxidative stress and cytokine production. Nuclear factor erythroid 2-related factor 2 (Nrf-2) is a vital transcription factor that regulates oxidative stress and inhibits inflammation. Studies have shown that Nrf-2 protects against radiation-induced lung inflammation and fibrosis. This review discusses the protective role of Nrf-2 in RILI and its possible mechanisms.

Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway.

OBJECTIVE: To observe the protective effect and mechanism of hydroxyl safflower yellow A (HSYA) from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were treated with oxygen-glucose deprivation reperfusion (OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations (1.25-160 µ mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 µ mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 ß, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3 (NLRP3), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt (CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1 (Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. RESULTS: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18, IL-1 ß, MCP-1, TNF-α and IL-6 (P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3, Caspase-1, GSDMD and GSDMD-N proteins (P<0.01). CONCLUSIONS: The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.

The predictive utility of cytokines, procalcitonin and C-reactive protein among febrile pediatric hematology and oncology patients with severe sepsis or septic shock.

Severe sepsis and septic shock are life-threatening for pediatric hematology and oncology patient receiving chemotherapy. Th1/Th2 cytokines, C-reactive protein (CRP), and procalcitonin (PCT) are all thought to be associated with disease severity. The aim of this study was to prospectively verify the utility of Th1/Th2 cytokines and compare them with PCT and CRP in the prediction of adverse outcomes. Data on patients were collected from January 1, 2011, to December 31, 2020. Blood samples were taken for Th1/Th2 cytokine, CRP, and PCT measurements at the initial onset of infection. Severe infection (SI) was defined as severe sepsis or septic shock. Th1/Th2 cytokine levels were determined by using flow cytometric bead array technology. In total, 7,735 febrile episodes were included in this study. For SI prediction, the AUCs of IL-6, IL-10 and TNF-α were 0.814, 0.805 and 0.624, respectively, while IL-6 and IL-10 had high sensitivity and specificity. IL-6 > 220.85 pg/ml and IL-10 > 29.95 pg/ml had high odds ratio (OR) values of approximately 3.5 in the logistic regression. Within the subgroup analysis, for bloodstream infection (BSI) prediction, the AUCs of IL-10 and TNF-α were 0.757 and 0.694, respectively. For multiorgan dysfunction syndrome (MODS) prediction, the AUC of CRP was 0.606. The AUC of PCT for mortality prediction was 0.620. In conclusion, IL-6 and IL-10 provide good predictive value for the diagnosis of SI. For children with SI, IL-10 and TNF-α are associated with BSI, while CRP and PCT are associated with MODS and death, respectively.

Prognostic performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal procalcitonin.

INTRODUCTION: It is important to predict adverse outcomes in febrile children with hematology/oncology diseases. Procalcitonin (PCT) is a promising biomarker for the prediction of infection severity, but further studies have revealed its performance in excluding adverse outcomes of infection. IL-6 and IL-10 were reported to have a close association with those infection outcomes. The aim of the study was to investigate the performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal PCT. METHODS: This was a retrospective study conducted in a tertiary children's hospital in China over the past ten years. Inflammatory biomarkers, including IL-6, IL-10, PCT and C-reactive protein (CRP), were detected at the onset of infection. Separate analyses were conducted in patients with neutropenia and without neutropenia. RESULTS: In total, 5987 febrile cases were enrolled. For patients with neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with bloodstream infection (BSI), gram-negative bacteremia (GNB) and severe sepsis (SS), but only IL-6 and IL-10 were predictive of GNB and SS. For patients without neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with BSI, GNB and SS, but no biomarkers were predictive of adverse outcomes. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis in patients with neutropenia. CONCLUSIONS: IL-6 and IL-10 could be predictors for GNB and SS in febrile patients with neutropenia and had some association with unfavorable outcomes in febrile patients without neutropenia. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis.

[A case of neonatal-onset type I hyperlipoproteinemia with bloody ascites]. / æ–°ç”Ÿå„¿æœŸèµ·ç— ä¼´è¡€æ€§è ¹æ°´çš„â 型高脂蛋白血症1例.

This report presents a case of a male infant, aged 32 days, who was admitted to the hospital due to 2 days of bloody stools and 1 day of fever. Upon admission, venous blood samples were collected, which appeared pink. Blood biochemistry tests revealed elevated levels of triglycerides and total cholesterol. The familial whole genome sequencing revealed a compound heterozygous variation in the LPL gene, with one variation inherited from the father and the other from the mother. The patient was diagnosed with lipoprotein lipase deficiency-related hyperlipoproteinemia. Acute symptoms including bloody stools, fever, and bloody ascites led to the consideration of acute pancreatitis, and the treatment involved fasting, plasma exchange, and whole blood exchange. Following the definitive diagnosis based on the genetic results, the patient was given a low-fat diet and received treatment with fat-soluble vitamins and trace elements, as well as adjustments to the feeding plan. After a 4-week hospitalization, the patient's condition improved and he was discharged. Follow-up showed a decrease in triglycerides and total cholesterol levels. At the age of 1 year, the patient's growth and psychomotor development were normal. This article emphasizes the multidisciplinary diagnosis and treatment of familial hyperlipoproteinemia presenting with symptoms suggestive of acute pancreatitis, including bloody ascites, in the neonatal period.

[Research progress in mechanism of puerarin in treating vascular dementia].

Vascular dementia(VD) is a condition of cognitive impairment due to acute and chronic cerebral hypoperfusion. The available therapies for VD mainly focus on mitigating cerebral ischemia, improving cognitive function, and controlling mental behavior. Achievements have been made in the basic and clinical research on the treatment of VD with traditional Chinese medicine(TCM) active components, including Ginkgo leaf extract, puerarin, epimedium, tanshinone, and ginsenoside. Most of these components have anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective effects, and puerarin demonstrates excellent performance in mitigating cholinergic nervous system disorders and improving synaptic plasticity. Puerarin, ginkgetin, and epimedium are all flavonoids, while tanshinone is a diterpenoid. Puerariae Lobatae Radix, pungent in nature, can induce clear Yang to reach the cerebral orifices and has the wind medicine functions of ascending, dispersing, moving, and scurrying. Puerariae Lobatae Radix entering collaterals will dredge blood vessels to promote blood flow, and that entering the sweat pore will open the mind, which is in line with the TCM pathogenesis characteristics of VD. This study reviews the progress in the mechanism of puerarin, the main active component of Puerariae Lobatae Radix, in treating VD. Puerarin can ameliorate cholinergic nervous system disorders, reduce excitotoxicity, anti-inflammation, inhibit apoptosis, alleviate oxidative stress injury, enhance synaptic plasticity, up-regulate neuroprotective factor expression, promote cerebral circulation metabolism, and mitigate Aß injury. The pathways of action include activating nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE), vascular endothelial growth factor(VEGF), extracellular regulated protein kinases(ERK), phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), Janus-activating kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3), AMP-activated protein kinase(AMPK), as well as inhibiting the tumor necrosis factor α(TNF-α), transient receptor potential melastatin 2(TRPM2)/N-methyl-D-aspartate receptor(NMDAR), p38 mitogen-activated protein kinase(p38 MAPK), Toll-like receptor 4(TLR4)/nuclear factor-kappaB(NF-κB), early growth response 1(Egr-1), and matrix metalloproteinase 9(MMP-9). By reviewing the papers about the treatment of VD by puerarin published by CNKI, Wanfang, VIP, PubMed, and Web of Science in the last 10 years, this study aims to support the treatment and drug development for VD.

[Characteristics and Influencing Factors of Greenhouse Fluxes from Urban Lawn].

As an important component of urban green spaces, greenhouse gas uptake or emissions from urban lawns cannot be ignored. However, studies of greenhouse gas fluxes from subtropical urban lawns are relatively sparse. The static chamber-gas chromatography method was applied to monitor the ground-air exchange fluxes of various greenhouse gases(CO2, CH4, N2O, and CO) in typical urban lawns of Hangzhou City. Our results showed that the average fluxes had significant seasonal cycles but ambiguous diurnal variations. The grassland and the soil(naked soil without vegetation coverage) acted as sources of atmospheric N2O, with the average fluxes of (0.66±0.17) and (0.58±0.20) µg·(m2·min)-1 for N2O, respectively; however, they were also sinks of CH4 and CO, with the average fluxes of (-0.21±0.078) and (-0.26±0.10) µg·(m2·min)-1 for CH4 and (-6.36±1.28) and (-6.55±1.69) µg·(m2·min)-1 for CO, respectively. The average CO2emission fluxes of urban grassland and soil were(5.28±0.75) and (4.83±0.91) mg·(m2·min)-1, respectively. The correlation analysis indicated that the CO2 and N2O fluxes of grassland and soil were negatively correlated with precipitation, whereas the CH4 and CO fluxes were positively correlated with it. There was no significant correlation between grassland CH4 fluxes and soil temperature, and N2O fluxes had a significant negative correlation with soil temperature; the other greenhouse gas fluxes showed a significant positive correlation with soil temperature. In addition, the seasonal variation in CO2 (R2=0.371 and 0.314) and N2O(R2=0.371 and 0.284) fluxes from both grassland and soil was affected by precipitation, whereas CO fluxes (R2=0.290 and 0.234) were mainly driven by soil temperature compared with the other greenhouse gases.

Surgery after combination therapy with a tyrosine kinase inhibitor and anti-PD-1 antibody in sarcomatoid hepatocellular carcinoma: case report and literature review.

Introduction: Although surgery is the preferred treatment for sarcomatoid hepatocellular carcinoma (SHC), the prognosis remains considerably poor due to early postoperative recurrence and metastasis. Reports on surgery after combined treatment with a tyrosine kinase inhibitor and anti-programmed cell death (PD)-1 antibody are unavailable. Case presentation: A 69-year-old male patient with SHC was admitted to our hospital for treatment of a liver tumor that was detected on ultrasonography. Abdominal computed tomography with triple-phase enhancement revealed a lesion in the right hepatic lobe that measured 86.0 mm × 75.0 mm × 71.0 mm. Biopsy revealed a pathological diagnosis of liver sarcoma or sarcomatoid carcinoma. The patient subsequently received transcatheter arterial chemo-embolization, as he did not consent to surgery. More than two months later, he received a combination of lenvatinib with camrelizumab, as computed tomography showed an increase in the lesion size (to 123.0 mm × 90.0 mm × 80.0 mm) and lateral growth posterior to the upper pole of the right kidney. Liver resection was performed after 6 months of systemic therapy; pathological examination confirmed a diagnosis of SHC and showed extensive necrosis of tumor cells. Combined treatment with lenvatinib and camrelizumab was continued for 6 months after surgery. The patient has survived for over 24 months after initial diagnosis and is currently tumor-free. Conclusion: Combined systemic therapy with a tyrosine kinase inhibitor and anti-PD-1 antibody may represent a feasible treatment strategy for improving resectability in cases of unresectable SHC. The outcomes with this combination may also be explored in cases of resectable SHC that have a high-risk of recurrence; this may improve the therapeutic effect.

[Mechanism of Buyang Huanwu Decoction in protecting ischemic myocardium by regulating platelet autophagy in rats with acute myocardial infarction].

This study explored the effects of Buyang Huanwu Decoction(BYHWD) on platelet activation and differential gene expression after acute myocardial infarction(AMI). SD rats were randomly divided into a sham-operated group, a model group, a positive drug(aspirin) group, and a BYHWD group. Pre-treatment was conducted for 14 days with a daily oral dose of 1.6 g·kg~(-1) BYHWD and 0.1 g·kg~(-1) aspirin. The AMI model was established using the high ligation of the left anterior descending coronary artery method. The detection indicators included myocardial infarct size, heart function, myocardial tissue pathology, peripheral blood flow perfusion, platelet aggregation rate, platelet membrane glycoprotein CD62p expression, platelet transcriptomics, and differential gene expression. The results showed that compared with the sham-operated group, the model group showed reduced ejection fraction and cardiac output, decreased peripheral blood flow, and increased platelet aggregation rate and CD62p expression, and activated platelets. At the same time, TXB_2 content increased and 6-keto-PGF1α content decreased in serum. Compared with the model group, BYHWD increased ejection fraction and cardiac output, improved blood circulation in the foot and tail regions and cardiomyocytes arrangement, reduced myocardial infarct size and inflammatory infiltration, down-regulated platelet aggregation rate and CD62p expression, reduced serum TXB_2 content, and increased 6-keto-PGF1α content. Platelet transcriptome sequencing results revealed that BYHWD regulated mTOR-autophagy pathway-related genes in platelets. The differential gene expression levels were detected using real-time quantitative PCR. BYHWD up-regulated mTOR, down-regulated autophagy-related FUNDC1 and PINK genes, and up-regulated p62 gene expression. The results demonstrated that BYHWD could regulate platelet activation, improve blood circulation, and protect ischemic myocardium in AMI rats, and its mechanism is related to the regulation of the mTOR-autophagy pathway in platelets.

Effect of auricular acupressure combined with acupuncture for juvenile pseudomyopia.

This retrospective study investigated the effect of auricular acupressure combined with acupuncture for juvenile pseudomyopia (JPM). In this retrospective study, we collected and analyzed a total of 66 eligible records of subjects with JPM. They were allocated into a treatment group (n = 33) and a control group (n = 33). All participants in both groups received auricular acupressure. Additionally, children in the treatment group also underwent acupuncture. The primary outcome was naked visual acuity (VA). It was performed using a standard E visual acuity chart. The secondary outcome was visual fatigue symptoms, as assessed by the College of Optometrists in Vision Development Quality of Life (COVD-QoL) questionnaire. All outcomes were analyzed before and after treatment. There were no significant differences regarding the naked VA and COVD-QoL scores before and after treatment between the 2 groups. However, there were significant differences regarding on naked VA (P < .01) and COVD-QoL scores (P < .01) within 2 groups compared before and after treatment. The findings of this study showed that both APP plus acupuncture and APP alone benefit children with JPM.

[Neonatal systemic pseudohypoaldosteronism type I]. / æ–°ç”Ÿå„¿å¤šè„å™¨åž‹å‡æ€§é†›å›ºé ®å‡å°‘ç—‡â 型.

An 18-day-old male infant was admitted to the hospital due to recurrent hyperkalemia for more than 10 days. The neonate had milk refusal and dyspnea. The blood gas analysis revealed recurrent hyperkalemia, hyponatremia and metabolic acidosis. Adrenocortical hormone replacement therapy was ineffective. Additional tests showed a significant increase in aldosterone levels. Family whole exome sequencing revealed that the infant had compound heterozygous in the SCNNIA gene, inherited from both parents. The infant was diagnosed with neonatal systemic pseudohypoaldosteronism type I. The infant's electrolyte levels were stabilized through treatment with sodium polystyrene sulfonate and sodium supplement. The infant was discharged upon clinical recovery. This study provides a focused description of differential diagnosis of salt-losing syndrome in infants and introduces the multidisciplinary management of neonatal systemic pseudohypoaldosteronism type I.

New advances in circulating tumor cell­mediated metastasis of breast cancer (Review).

Breast cancer stands as the most prevalent form of cancer affecting women, with metastasis serving as a leading cause of mortality among patients with breast cancer. Gaining a comprehensive understanding of the metastatic mechanism in breast cancer is essential for early detection and precision treatment of the disease. Circulating tumor cells (CTCs) play a vital role in this context, representing cancer cells that detach from tumor tissues and enter the bloodstream of cancer patients. These cells travel in the blood circulation as single cells or clusters. Recent research has shed light on the enhanced metastatic potential of CTC clusters compared to single CTCs, despite their limited occurrence. The aim of the present review was to explore recent findings on CTCs with a particular focus on the clustering phenomenon of CTCs observed in breast cancer. Additionally, the present review delved into the comparison between single CTCs and CTC clusters regarding their implications for the treatment and prognosis of patients diagnosed with metastatic breast cancer. By examining the role and mechanisms of CTCs in breast cancer metastasis, the present review provided an improved understanding of CTCs and their significance in early detection of breast cancer metastasis through peripheral blood analysis. Moreover, it contributed to the comprehension of cancer prognosis and prediction by highlighting the implications of CTCs in these aspects. Ultimately, the present study seeks to advance knowledge in the field and pave the way for improved approaches to breast cancer management.

The Correlation between Genotype Richness of Submerged Macrophytes and Periphyton Biomass: A Mesocosm Study Based on Five Dominant Submerged Macrophytes from Yangtze River.

Submerged macrophyte and periphyton are main primary producers which strongly interact with each other in clear water shallow lakes. In this study, the effects of genetic variation of the macrophyte species on periphyton biomass were studied in five submerged species. A two-year mesocosm study was conducted with four levels of genetic diversity (1, 4, 8 and 16 genotypes) for each submerged macrophyte, including 1600 individuals and 320 boxes in 20 mesocosms. Of the five submerged species, only Vallisneria spinulosa showed a positive correlation between its levels of genotype richness and the periphyton biomass. The correlation between genetic distance of genotypes and periphyton biomass was tested, which varied with the difference of seasons and species. In summary, we found that in freshwater mesocosms, the genetic diversity of submerged macrophytes may play a role in regulating the periphyton biomass, but the interaction between genetic diversity of macrophytes and periphyton biomass was not straightforward. This study will provide new insights into the interaction dynamics between the two primary producers in shallow lakes.