Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.@*METHODS@#A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed.@*RESULTS@#FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05).@*CONCLUSION@#FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

Finite element analysis of cervical intervertebral discs after removing different ranges of uncinate processes / 解剖学报

Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C

Down-regulation of METTL5 inhibits proliferation, migration and invasion of triple-negative breast cancer cells through Wnt/6-catenin signaling pathway / 中国药理学通报

Aim To investigate the role and potential mechanism of methyltransferase-like 5 (METTL5) in triple-negative breast cancer (TNBC) . Methods The expression of METTL5 in TNBC tumor tissues and cell lines was detected by immunohistochemistry and Western blot. After shRNA targeting METTL5 (shRNAMETTL5) was transfected into TNBC cells, cell proliferation, migration and invasion were detected by CCK-8, colony formation, wound healing and Transwell assays, respectively. Western blot was used to detect the expression of Wnt/p-catenin signaling-related key proteins. A xenograft tumor model was constructed to verify the effect of METTL5 knockdown on the growth of TNBC cells and Wnt/p-catenin signaling activity in vivo. Results The expression of METTL5 was up-regulated in TNBC tumor tissues and cell lines (P < 0. 01) . Knockdown of METTL5 significantly inhibited the proliferation, migration and invasion of TNBC cells and reduced the expression of Wnt/p-catenin signaling molecules (3-catenin, cyclin Dl, matrix metalloproteinase (MMP) -2 and MMP-7 (all P < 0. 01) . Knockdown of METTL5 reduced tumor growth and Wnt/pcatenin signaling activity in vivo. Conclusions Knockdown of METTL5 can inhibit the proliferation, migration and invasion of TNBC cells, which may be related to the inhibition of Wnt/p-catenin signaling pathway.

A preliminary study on salivary microbiota of patients with laryngopharyngeal reflux / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the characteristics of salivary microbiota in patients with laryngopharyngeal reflux (LPR). Methods: A case-control study was applied to enroll 60 patients and healthy subjects who were outpatients of the Department of Otorhinolaryngology Head and Neck Surgery of the Eighth Medical Center of the PLA General Hospital from December 2020 to March 2021, including 35 males and 25 females, aged from 21 to 80 (33.75±11.10) years. Thirty patients with suspected laryngopharyngeal reflux were selected as study group and thirty healthy volunteers without pharyngeal symptoms were selected as control group. Their salivary samples were collected, and the salivary microbiota was detected and analyzed by 16S rDNA sequencing. SPSS 18.0 software was used for statistical analysis. Results: There was no significant difference in the diversity of salivary microbiota between the two groups. At the phylum classification level, the relative abundance of Bacteroidetes in the study group was higher than that in the control group[37.86(31.15, 41.54)% vs 30.24(25.51, 34.18)%,Z=-3.46,P<0.01]. And the relative abundance of Proteobacteria in the study group was lower than that in the control group [15.76(11.81, 20.17)% vs 20.63(13.98, 28.82)%, Z=-1.98,P<0.05]. At the genus level, the relative abundance of Prevotella, Lactobacillus, Parascardovia and Sphingobium in the study group was higher than that in the control group(Z values were-2.92, -2.69, -2.05, -2.31, respectively, P<0.05).And the relative abundance of Streptococcus, Cardiobacterium, Klebsiella and Uruburuella of study group was lower than that of control group(Z values were -2.43, -2.32, -2.17, -2.32, respectively, P<0.05). LEfSe difference analysis showed that there were 39 bacteria with significant differences between the two groups, including Bacteroidetes, Prevotellaceae and Prevotella, which were enriched in the study group, and Streptococcaceae, Streptococcus and other taxa, which were enriched in the control group(P<0.05). Conclusion: The changes of the microflora in the saliva between LPR patients and healthy people suggest that the dysbacteriosis might exist in LPR patients, which may play an important role in the pathogenesis and development of LPR.

Exposure level of neonicotinoid pesticides and their metabolites in pregnant women in the suburb of Shanghai / 中华预防医学杂志

In 2021, a total of 151 pregnant women were selected from the suburb of Shanghai. A questionnaire survey was conducted to obtain data about maternal age, gestational week, total annual household income, education level and passive smoking among pregnant women and one spot urine was collected. The concentrations of eight neonicotinoid pesticides and four metabolites in urine were measured by ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry. The differences in detection frequencies and concentrations of neonicotinoid pesticides and their metabolites among pregnant women with different characteristics were compared, and the influencing factors of the detection of neonicotinoid pesticides in urine were analyzed. The results showed that at least one neonicotinoid pesticide was detected in 93.4% (141 samples) of urine samples. The detection frequencies of N-desmethyl-acetamiprid, clothianidin, thiamethoxam, and N-desmethyl-clothianidin were high, about 78.1% (118 samples), 75.5% (114 samples), 68.9% (104 samples), and 44.4% (67 samples), respectively. The median concentration of the sum of all neonicotinoid pesticides was 2.66 μg/g. N-desmethyl-acetamiprid had the highest detection concentration with a median concentration of 1.04 μg/g. A lower urinary detection frequency of imidacloprid and its metabolites was seen in pregnant women aged 30-44 years [OR (95%CI): 0.23 (0.07-0.77)]. A higher detection frequency of clothianidin and its metabolites was seen in pregnant women with per capita annual household income≥100 000 yuan [OR (95%CI): 6.15 (1.56-24.28)]. There was widespread exposure to neonicotinoid pesticides and their metabolites in pregnant women from the suburb of Shanghai, which might pose potential health risks to pregnant women, and maternal age and household income were potential influencing factors of the exposure to neonicotinoid pesticides.

Effect of Yunkang Oral Solution on pregnant mice with spleen deficiency syndrome / 中国中药杂志

This study aimed to investigate the therapeutic effect of Yunkang Oral Solution on the improvement of spleen deficiency and pregnancy outcomes in pregnant mice with spleen deficiency syndrome induced by irregular diet and over consumption of cold and bitter foods. To simulate human irregular diet and over consumption of cold and bitter foods leading to spleen deficiency, the pregnant mice with spleen deficiency syndrome were prepared using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, spleen deficiency-related indicators and diarrhea-related parameters were measured. Gastric and intestinal motility(gastric emptying rate and intestinal propulsion rate) were evaluated. The levels of serum ghrelin, growth hormone(GH), gastrin(Gas), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-c), chorionic gonadotropin β(β-CG), progesterone(P), and estradiol(E_2) were measured. Intestinal barrier function in pregnant mice with spleen deficiency syndrome was assessed. Conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length were calculated. The results showed that Yunkang Oral Solution significantly improved spleen deficiency-related indicators and diarrhea in pregnant mice with spleen deficiency syndrome, increased gastric emptying rate and intestinal propulsion rate, elevated the levels of gastrointestinal hormones(ghrelin, GH, and Gas) in the serum, and reduced lipid levels(TC and LDL-c), thereby improving lipid metabolism disorders. It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin and claudin-1 in colonic tissues, thereby alleviating intestinal barrier damage. Yunkang Oral Solution also regulated the levels of pregnancy hormones(β-CG, P, and E_2) in the serum of pregnant mice with spleen deficiency syndrome. Moreover, it increased the conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length. These findings suggest that Yunkang Oral Solution can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.

Matrine inhibits inflammatory response induced by TNF-α in human umbilical vein endothelial cells through miR-25-3p-mediated Klf4 pathway / 中国中药杂志

This study aimed to analyze the effect of matrine on tumor necrosis factor-α(TNF-α)-induced inflammatory response in human umbilical vein endothelial cells(HUVECs) and explore whether the underlying mechanism was related to the miR-25-3p-mediated Krüppel-like factor 4(Klf4) pathway. The HUVEC cell inflammation model was induced by TNF-α stimulation. After 24 or 48 hours of incubation with different concentrations of matrine(0.625, 1.25, and 2.5 mmol·L~(-1)), CCK-8 assay was used to detect cell proliferation. After treatment with 2.5 mmol·L~(-1) matrine for 48 h, the expression of TNF-α, interleukin-6(IL-6), interleukin-1β(IL-1β), and Klf4 mRNA and miR-25-3p was detected by real-time fluorescence-based quantitative PCR, and the protein expression of TNF-α, IL-6, IL-1β, and Klf4 was detected by Western blot. The anti-miR-25-3p was transfected into HUVECs, and the effect of anti-miR-25-3p on TNF-α-induced cell proliferation and inflammatory factors was detected by the above method. The cells were further transfected with miR-25-3p and incubated with matrine to detect the changes in proliferation and expression of related inflammatory factors, miR-25-3p, and Klf4. The targeting relationship between miR-25-3p and Klf4 was verified by bioinformatics analysis and dual luciferase reporter gene assay. The results displayed that matrine could inhibit TNF-α-induced HUVEC proliferation, decrease the mRNA and protein expression of TNF-α, IL-6, and IL-1β, increase the mRNA and protein expression of Klf4, and reduce the expression of miR-25-3p. Bioinformatics analysis showed that there were specific complementary binding sites between miR-25-3p and Klf4 sequences. Dual luciferase reporter gene assay confirmed that miR-25-3p negatively regulated Klf4 expression in HUVECs by targeting. The inhibition of miR-25-3p expression can reduce TNF-α-induced cell proliferation and mRNA and protein expression of TNF-α, IL-6, and IL-1β. MiR-25-3p overexpression could reverse the effect of matrine on TNF-α-induced cell proliferation and the mRNA and protein expression of TNF-α, IL-6, IL-1β, and Klf4. This study shows that matrine inhibits the inflammatory response induced by TNF-α in HUVECs through miR-25-3p-mediated Klf4 pathway.

Effects of growth patterns and years on quality of Saposhnikoviae Radix samples / 中国中药杂志

This study aims to reveal the effects of different growth patterns and years on the quality of Saposhnikoviae Radix samples. The apparent colors of the powder samples were quantified by a colorimeter, and the total color values(E~*ab) were calculated. The content of prim-O-glucosylcimifugin, cimifugin, 4'-O-β-D-glucosyl-5-O-methylvisamminol, sec-O-glucosylhamaudol, and 3'-O-angeloylhamaudol in the samples was simultaneously determined by high performance liquid chromatography(HPLC). Cluster analysis, principal component analysis, partial least squares discriminant analysis, and Pearson correlation analysis were performed to analyze the powder chromatic values and the content of 5 components. The results showed that the E~*ab values of the samples were in the order of wild group<multiple-year-old group<one-year-old group. The content of cimifugin, sec-O-glucosylhamaudol, and 3'-O-angeloylhamaudol in the wild group was significantly higher than that in the multiple-year-old and one-year-old groups. The results of multivariate statistical analysis showed that the quality of multiple-year-old group varied greatly. The quality of the multiple-year-old samples was close to that of the wild group and better than that of the one-year-old group. The variable importance in the projection(VIP) values of b~*, 3'-O-angeloylhamaudol content, E~*ab, and L~* were all larger than 1, and that of cimifugin content was close to 1. The E~*ab value was negatively correlated with the content of prim-O-glucosylcimifugin, cimifugin, sec-O-glucosylhamaudol, and 3'-O-angeloylhamaudol, while it had no linear correlation with the 4'-O-β-D-glucosyl-5-O-methylvisamminol content. The growth patterns and years had different effects on the quality of Saposhnikoviae Radix samples. The chromatic values of Saposhnikoviae Radix and the content of 5 components can be used to evaluate the quality of Saposhnikoviae Radix, and 3'-O-angeloylhamaudol and cinmifugin can be considered as markers for the quality control of Saposhnikovia divaricata during the growing process.

Clinical Analysis of Colistin Sulfate in the Treatment of Hematonosis Infected by Multidrug-Resistant Gram-Negative Bacteria / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of colistin sulfate in the treatment of hematonosis patients infected by multidrug-resistant (MDR) gram-negative bacteria (GNB), and discuss the possible factors that affect the efficacy of colistin sulfate.@*METHODS@#The clinical data of 85 hematologic patients infected with MDR GNB in the Soochow Hopes Hematonosis Hospital from April 2022 to November 2022 were collected and divided into clinically effective group with 71 cases and ineffective group with 14 cases according to the therapeutic efficacy of colistin sulfate. The age, gender, type of hematologic disease, status of hematopoietic stem cell transplantation, infection sites, type of pathogen, timing of administration, daily dose and duration of colistin sulfate, and combination with other antibacterial agents of patients in two groups were compared. Logistic regression was used to analyze on the meaningful variables to study the influencing factors of colistin sulfate. The adverse reactions of colistin sulfate were also evaluated.@*RESULTS@#There were no significant differences in age, gender, type of hematologic disease, hematopoietic stem cell transplantation status, infection sites and pathogen type between the effective group and the ineffective group (P>0.05). Compared with the medication time more than 7 days, meropenem used within 7 days in the clinical effective group, and timely replacement with colistin sulfate could obtain better efficacy, the difference was statistically significant (P=0.018). The duration of tigacycline before colistin sulfate did not affect the efficacy, and there was no significant difference in efficacy between the effective and ineffective groups. The therapeutic effect of colistin sulfate at daily dose of 500 000 U q8h was better than that of 500 000 U q12h, the difference was statistically significant (P=0.035). The time of colistin sulfate use in the clinically effective group was longer than that in the ineffective group, which had a statistical difference (P=0.003). Compared with the clinical ineffective group, the efficacy of combination regimens with colistin sulfate was better than that of colistin sulfate monotherapy, and the difference was statistically significant (P=0.013). Multivariate logistic regression analysis was performed on the indicators with statistical differences in the two groups of patients, which suggested that the use time of colistin sulfate (B: 2.358; OR: 10.573; CI: 1.567-71.361; P=0.015) and the combination of colistin sulfate (B: 1.720; OR: 5.586; CI: 1.210-25.787; P=0.028) were influential factors in the efficacy of colistin sulfate. During the treatment, the incidence of nephrotoxicity, hepatotoxicity and peripheral neurotoxicity were 5.9%, 1.2% and 1.2%, respectively.@*CONCLUSION@#The use of colistin sulfate improves the clinical efficacy of MDR GNB infections in hematological patients, and the timing of colistin sulfate administration and the combination of drugs are independent factors affecting its clinical efficacy, and the safety during treatment is high.

Icariin Ameliorates Efferocytosis Dysfunction of Alveolar Macrophages Stimulated by Cigarette Smoke Extract via PPARγ Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of icariin in ameliorating efferocytosis dysfunction and inflammatory response of alveolar macrophages induced by cigarette smoke extract via the peroxisome proliferator-activated receptor gamma （PPARγ） signaling pathway. MethodThe untreated rat alveolar macrophages （NR8383） were taken as the blank group. The NR8383 cells treated with 10% cigarette smoke extract were divided into model， low-， medium-， and high-dose （10， 20， 40 μmol·L-1） icariin， PPARγ inhibitor， and PPARγ inhibitor + low-， medium-， and high-dose icariin groups. Alamar blue colorimetry was employed to examine the proliferation and toxicity of icariin on NR8383 cells. The efferocytosis rate of NR8383 cells was detected by flow cytometry. Enzyme-linked immunosorbent assay was employed to measure the levels of tumor necrosis factor-alpha （TNF-α）， transforming growth factor-β1 （TGF-β1）， and milk fat globule-epidermal growth factor 8 （MFG-E8）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were employed to determine the protein and mRNA levels， respectively， of PPARγ， CD36， and RAS-related C3 botulinum toxin substrate 1 （Rac1）. ResultThe efferocytosis dysfunction model of NR8383 was established with the cigarette smoke extract. Compared with the blank control group， the model group showed decreased efferocytosis rate （P<0.05）， elevated TNF-α level （P<0.05）， lowered TGF-β1 and MFG-E8 levels （P<0.01）， and down-regulated mRNA and protein levels of PPARγ， CD36， and Rac1 （P<0.05， P<0.01）. Compared with the model group， the treatment with icariin increased the efferocytosis rate （P<0.05， P<0.01）， lowered the TNF-α level （P<0.01）， elevated TGF-β1 and MFG-E8 levels （P<0.05）， and up-regulated the protein and mRNA levels of PPARγ， CD36， and Rac1 （P<0.05， P<0.01）. Compared with icariin alone， PPARγ inhibitor + icariin decreased the efferocytosis rate （P<0.05） and down-regulated the protein and mRNA levels of PPARγ （P<0.05， P<0.01）. In addition， PPARγ inhibitor + low-dose icariin down-regulated the protein level of CD36 （P<0.01） and PPARγ inhibitor + low-/medium-dose icariin up-regulated the protein level of Rac1 （P<0.05）. ConclusionIcariin ameliorates the cigarette smoke extract-induced efferocytosis dysfunction of alveolar macrophage by regulating the PPARγ signaling pathway and cytoskeletal structure rearrangement.

Effect of radiofrequency radiation from 5G mobile phone on blood-brain barrier in mice / 中华放射医学与防护杂志

Objective:To investigate the effect of radiofrequency radiation (RF) from 5G mobile phone communication frequency bands (3.5 GHz and 4.9 GHz) on the permeability of the blood-brain barrier (BBB) in mice.Methods:A total of 24 healthy adult male C57BL/6 mice (6-8 weeks old) were randomly divided into Sham, 3.5 GHz RF and 4.9 GHz RF groups, and 8 mice in each group. Mice in the RF groups were systemically exposed to 5G cell phone radiation for consecutive 35 d(1 h/d) with 50 W/m 2 power density. The BBB permeability of mice was detected by Evans Blue (EB) fluorescence experiment. The expression levels of the BBB tight junction-related proteins (ZO-1, occludin and claudin-11) and the gap junction-related protein Connexin 43 were determined by Western blot. Results:The number of spots, fluorescence intensity and comprehensive score of EB were significantly increased in 3.5 GHz RF group and 4.9 GHz RF group compared with the Sham group ( t=12.98, 17.82, P<0.001). Compared with the Sham group, the content of S100B in mouse serum was significantly increased in 3.5 GHz RF group and 4.9 GHz RF group ( t=19.34, 14.68, P<0.001). The BBB permeability was increased in the RF group. The expression level of occludin protein was significantly reduced in the 3.5 GHz RF group ( t=-3.13, P<0.05), and this decrease was much profound in the 4.9 GHz RF group ( t=-6.55, P<0.01). But the protein levels of ZO-1, Claudin-11 and Connexin 43 in the cerebral cortex of the RF groups had no significantly difference in comparison with the Sham group( P>0.05). Conclusions:The continuous exposure of mobile phone RF at 3.5 GHz or 4.9 GHz for 35 d (1 h/d) induces an increase of BBB permeability in the mouse cerebral cortex, perhaps by reducing the expression of occludin protein.

Relationship between cerebrovascular variation and the occurrence and recurrence of cerebral infarction / 中华行为医学与脑科学杂志

Objective:To investigate the relationship between cerebrovascular variation and the occurrence and recurrence of cerebral infarction, and provide a theoretical basis for the precise prevention and treatment of cerebral infarction.Methods:Totally 13 939 patients who underwent magnetic resonance imaging(MRI) and magnetic resonance angiography(MRA) examination at the Second Affiliated Hospital of Shandong First Medical University from January 2020 to December 2021 were grouped according to clinical symptoms combined with the imaging report, including 4 412 cases in the cerebral infarction group and 9 527 cases in the control group.2 048 patients in the cerebral infarction group were eventually enrolled in the study according to the inclusion and exclusion criteria, including 1 479 cases of initial cerebral infarction and 569 cases of recurrent cerebral infarction.SPSS 25.0 statistical software was used for data analysis.The χ2 test was used to compare the incidence of cerebral infarction with different cerebrovascular variations.Univariate analysis of suspected risk factors for recurrent cerebral infarction was performed with χ2 test, nonparametric test and t test.The binary logistic regression was used to analyze independent risk factors of recurrent cerebral infarction. Results:The incidence of cerebral infarction in the dual-system cerebrovascular variant patients, the single-system cerebrovascular variant patients, and the non-cerebrovascular variant patients were 40.9%, 30.7% and 31.8% respectively.The incidence of cerebral infarction in the dual-system cerebrovascular variant patients was the highest compared with those in the single-system cerebrovascular variant patients and the non-cerebrovascular variant patients (both P<0.05). The incidence rates of embryonic posterior cerebral artery, vertebral artery dominance, and bilateral common origin anterior cerebral arteries were 14.09%, 10.76% and 5.32%, respectively.The incidence of bilateral common origin anterior cerebral arteries in the cerebral infarction group was significantly higher than that in the control group and the difference was statistically significant.Patients with cerebral infarction who were familial aggregation ( OR=2.207, 95% CI=1.591-3.062), hyperhomocysteinemia ( OR=1.262, 95% CI=1.014-1.570), hypertension ( OR=1.461, 95% CI=1.114-1.918), diabetes mellitus ( OR=1.348, 95% CI=1.072-1.694), coronary heart disease ( OR=1.491, 95% CI=1.196-1.858) were more likely to recurrent cerebral infarction ( P<0.05), and patients with cerebral infarction had a significantly increased risk of recurrent cerebral infarction with age ( OR=1.031, 95% CI=1.020-1.042, P<0.05). Conclusion:Dual-system cerebrovascular variation and bilateral common origin anterior cerebral arteries are risk factors for cerebral infarction.

Sleep deprivation aggravates cognitive impairment in septic rats by activating neuronal glycolytic isoenzyme PFKFB3 / 中华危重病急救医学

Objective:To evaluate the effect of sleep deprivation on cognitive function in septic rats and its relationship with neuronal glycolysis isoenzyme phosphofructokinase-2/fructose-2,?6-diphosphatase 3 (PFKFB3).Methods:Fifty-six healthy male Sprague-Dawley (SD) rats were randomly divided into 4 groups ( n = 14): control group (Con group), sepsis group (LPS group), sepsis+sleep deprivation group (LPS+SD group), sepsis+sleep deprivation+glycolysis inhibitor 3-PO treatment group (LPS+SD+3-PO group). The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) 10 mg/kg. Rats in LPS+SD group were treated with sleep deprivation using a sleep deprivation instrument 24 hours after LPS injection. The LPS+SD+3-PO group was intraperitoneally injected with LPS for 24 hours, and then injected with 3-PO 50 mg/kg, followed by sleep deprivation. Novel object recognition experiments were performed 72 hours after LPS injection. Subsequently, blood and brain tissue samples were collected. The contents of lactate (Lac), reactive oxygen species (ROS) and serum tumor necrosis factor-α(TNF-α), neuron-specific enolase (NSE), pyruvate in brain tissue were detected by enzyme-linked immunosorbent assay (ELISA). Then, the lactate/pyruvate ratio was calculated. Na +-K +-ATPase activity in brain tissue was detected by colorimetry. Morphological changes in hippocampus were detected by hematoxylin-eosin (HE) staining. And the protein expression levels of PFKFB3, ZO-1 and cleaved caspase-3 were measured by Western blotting. Results:Compared with Con group, the novel object recognition index of LPS group was decreased, the levels of NSE, TNF-α, lactate/pyruvate ratio in serum and the levels of Lac, ROS and dry-wet weight ratio in brain tissue were significantly increased, Na +-K +-ATPase activity in brain tissue was decreased, the protein expressions of PFKFB3, caspase-3 were up-regulated, ZO-1 expression was down-regulated, and the neurons in hippocampus were slightly degenerated. Compared with LPS group, the novel object recognition index of LPS+SD group was further decreased [(39.4±5.3)% vs. (54.5±7.6)%)], serum NSE, TNF-α, lactate/pyruvate ratio and brain tissue Lac, ROS, dry-wet weight ratio were further increased [NSE (μg/L): 3.21±0.42 vs. 2.55±0.36, TNF-α (ng/L): 139.4±19.7 vs. 92.2±13.5, lactate/pyruvate ratio: 29.7±5.5 vs. 19.2±4.2, Lac (μmol/g): 19.51±2.33 vs. 11.34±1.52, ROS (kU/g): 117.4±18.7 vs. 78.2±11.8, dry-wet weight ratio: (81.3±9.2)% vs. (64.3±6.6)%], and Na +-K +-ATPase activity was further decreased (mmol·L -1·h -1: 1.88±0.34 vs. 2.91±0.39), the protein expressions of PFKFB3, caspase-3 were further up-regulated and ZO-1 expression was further down-regulated (PFKFB3/β-actin: 0.80±0.11 vs. 0.45±0.07, caspase-3/β-actin: 0.71±0.09 vs. 0.37±0.05, ZO-1/β-actin: 0.31±0.05 vs. 0.61±0.08). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly aggravated. Compared with LPS+SD group, the novel object recognition index of LPS+SD+3-PO group was increased [(50.8±5.9)% vs. (39.4±5.3)%], NSE, TNF-α, lactate/pyruvate ratio of serum and Lac, ROS, dry-wet weight ratio of brain tissue were significantly decreased [NSE (μg/L): 2.60±0.33 vs. 3.21±0.42, TNF-α (ng/L): 103.7±18.3 vs. 139.4±19.7, lactate/pyruvate ratio: 17.4±5.1 vs. 29.7±5.5, Lac (μmol/g): 13.68±2.02 vs. 19.51±2.33, ROS (kU/g): 86.9±14.5 vs. 117.4±18.7, dry-wet weight ratio: (67.7±6.9)% vs. (81.3±9.2)%], and Na +-K +-ATPase activity was increased (mmol·L -1·h -1: 2.82±0.44 vs. 1.88±0.34). The protein expressions of PFKFB3, caspase-3 were down-regulated and ZO-1 expression was up-regulated (PFKFB3/β-actin: 0.50±0.06 vs. 0.80±0.11, caspase-3/β-actin: 0.43±0.06 vs. 0.71±0.09, ZO-1/β-actin: 0.52±0.06 vs. 0.31±0.05). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly improved. Conclusions:Sleep deprivation could aggravate neuroinflammation, neuronal degeneration and apoptosis in septic rats, resulting in destruction of blood-brain barrier and cognitive impairment. 3-PO treatment significantly alleviate the injury and degeneration of hippocampal neurons in septic rats, inhibit neuroinflammation and apoptosis, and improve cognitive dysfunction, which may be related to the inhibition of glycolytic isoenzyme PFKFB3.

Epidemiological investigation of adult thyroid diseases in urban and rural areas of Hebei Province / 中华地方病学杂志

Objective:To study the prevalence and distribution of adult thyroid diseases in urban and rural areas of Hebei Province.Methods:A multi-stage stratified cluster sampling method was used to select Renqiu City and Licun Town, Luquan City of Hebei Province as the urban and rural survey sites, respectively. Questionnaire survey, physical examination and thyroid B ultrasound examination were conducted on local permanent residents (≥ 5 years of residencies) over 18 years old. The fasting venous blood sample was collected to determine the serum thyroid function indicaters.Results:A total of 2 650 adults were surveyed, including 1 393 urban residents and 1 257 rural residents (1 357 males and 1 293 females). A total of 435 patients with thyroid diseases were diagnosed, the detection rate was 16.42%. There were seven thyroid diseases, including subclinical hypothyroidism (60.92%, 265/435), Hashimoto's thyroiditis (34.02%, 148/435), hypothyroidism (4.83%, 21/435), simple goiter (3.22%, 14/435), hyperthyroidism (2.53%, 11/435), subclinical hyperthyroidism (2.53%, 11/435), and thyroid cancer (1.84%, 8/435). The detection rates of thyroid diseases in urban and rural areas were 21.18% (295/1 393) and 11.14% (140/1 257), respectively. The detection rates of thyroid diseases in males and females were 11.42% (155/1 357) and 21.66% (280/1 293), respectively. The detection rates of thyroid diseases in 18-< 30, 30-< 40, 40-< 50, 50-< 60 and ≥60 years old were 13.46% (91/676), 14.81% (81/547), 15.42% (89/577), 20.94% (85/406) and 20.05% (89/444), respectively. There were statistically significant differences between different areas, gender and age groups (χ 2 = 48.54, 50.53, 14.68, P < 0.05). Conclusions:The detection rate of subclinical hypothyroidism in adults in urban and rural areas of Hebei Province is relatively high, followed by Hashimoto's thyroiditis. Attention should be paid to the screening, evaluation, and intervention of thyroid function among urban female populations.

Meta analysis of the efficacy of umbilical laparoendoscopic single-site surgery and conventional laparoscopic appendectomy in the treatment of pediatric acute appendicitis / 中华内分泌外科杂志

Objective:To analyze the effects of umbilical laparoendoscopic single-site surgery (U-LESS) and conventional laparoscopic appendectomy (CLS) on the treatment of acute appendicitis in children by using Meta-analysis. To evaluate the effectiveness and safety of U-LESS in treating acute appendicitis in children.Methods:The English databases Pubmed, Web of Science, the Cochrane Library, Clinical trials, CNKI, Weipu Database, Wanfang Medical Network Database, CBM literature and other Chinese databases were retrieved, and the relevant literature of the comparative study of U-LESS and CLS in the treatment of pediatric acute appendicitis was found, and the quality analysis and application of the selected comparative studies were carried out. RevMan5.3 and stata software were employed to compare the operation time, intraoperative blood loss, postoperative exhaust time, postoperative intestinal recovery time, incision length, postoperative hospital stay time, postoperative complications, etc. of different surgical procedures.Results:A total of 19 literature were included in this study, and a total of 2133 cases were included, including 1021 cases in the U-LESS group and 1112 cases in the CLS group, all of which were retrospective case-control studies. Meta analysis showed that the operation time in U-LESS was shorter than that in CLS (95%CI [-9.05, -3.17], Z=4.07, P<0.001) , and the intraoperative bleeding volume of U-LESS was less than that of CLS (95%CI [-15.28, -5.01], Z=3.87, P<0.001) , incision length was shorter in U-LESS than in CLS (95%CI [-1.40, -1.27], Z=39.30, P<0.001) , the postoperative exhaust time of U-LESS was shorter than that of CLS (95%CI [-8.63, -5.89], Z=10.37, P<0.001) , and the recovery time after U-LESS was shorter than that after CLS (95% CI, 95% CI, P<0.001) . U-LESS and CLS did not differ significantly in postoperative length of stay (95%CI [-1.33, -0.64], Z=5.61, P<0.001) . U-LESS had fewer postoperative complications compared with CLS (95%CI [0.24,0.52], Z=5.27, P<0.001) . Conclusion:For pediatric acute appendicitis, U-LESS is safe and feasible, and has the advantages of shortening the operation time and reducing intraoperative bleeding.

Study on network pharmacology of Polygalae Radix- Acori Tatarinowii Rhizoma medicinal pair for depression and Alzheimer disease with the same treatment / 国际中医中药杂志

Objective:To explore the molecular mechanism of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair for depression and Alzheimer disease (AD) with the same treatment through network pharmacology. Methods:Effective components of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair were retrieved from TCMSP, TCMID and ETCM databases. The disease targets of depression and AD were retrieved from GeneCards, TTD and CTD databases. Targets of action of drugs on active components were predicted through SwissTargetPrediction, and then the intersection targets of medicinal pair and the diseases were taken. Cytoscape 3.6.1 was used to construct the interaction network of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair on "component-common target-disease". The enrichment analysis of GO function and KEGG pathway was carried out with the help of Metascape platform, and molecular docking verification was carried out. Results:Through searching the databases and literature, 78 compounds in Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair were obtained, corresponding to 41 targets of different diseases with the same treatment. The GO function was mainly concentrated in response to lipopolysaccharide and cellular response to nitrogen compound. The KEGG pathway was mainly concentrated in lipid and atherosclerosis, calcium signaling pathway, serotonergic synapse, insulin resistance and so on. The core targets were PTGS2, ESR2, etc. Molecular docking showed that most of the core components could form stable conformation with the core targets. Conclusions:Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair has the characteristics of multi-component, multi-target and multi-pathway in the same treatment of depression and AD. Through their core components of senegenin, 1-carbobutoxy-β-carboline, 6-hydroxy-1,2,3,7-tetramethoxyxanthone, kaempferol and etc., the pair can act on PTGS2 and other targets, regulate lipid and atherosclerosis, calcium signaling pathway, serotonergic synapse, insulin resistance and so on, and play a therapeutic role in depression and Alzheimer's disease with the same treatment.

Prognostic predictors of immunotherapy in patients with small cell lung cancer / 国际肿瘤学杂志

The emergence of immune checkpoint inhibitors holds new promise for patients with small cell lung cancer. Studies have found that PD-L1 expression, tumor mutation burden, genomic characteristics, peripheral blood parameters and other indicators can be used as prognostic predictors in patients with small cell lung cancer receiving immunotherapy. Further exploration and evaluation of relevant predictors can provide a reference for screening patients with potential benefits of immunotherapy.

Liraglutide inhibits high glucose-induced cardiomyocyte hypertrophy via modulating autophagy and Na / 中国药理学通报

Aim To investigate the mechanism through which liraglutide (LRG) inhibited high glucose (HG)-induced cardiomyocyte hypertrophy. Methods Cultured H9c2 were divided into control (CON) group, HG group, low-, middle- and high-dose LRG (LRG-L, LRG-M and LRG-H) groups, LRG-H + autophagy inhibitor trimethyladenine (3-MA) group. The relative cell surface change was assessed phalloidin staining. Membrane bound Na, K

BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical models / 医学前沿

OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.

Platelet Transfusion Strategies for MASPAT-Matched Platelet Transfusion Failed Patient with Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the causes of ineffectiveness of platelet transfusion with monoclonal antibody solid phase platelet antibody test (MASPAT) matching in patients with allogeneic hematopoietic stem cell transplantation and explore the strategies of platelet transfusion.@*METHODS@#A case of donor-specific HLA antibodies (DSA) induced by transfusion which ultimately resulted in transplantation failure and ineffective platelet transfusion with MASPAT matching was selected, and the causes of ineffective platelet transfusion and platelet transfusion strategy were retrospectively analyzed.@*RESULTS@#The 32-year-old female patient was diagnosed as acute myeloid leukemia (high risk) in another hospital with the main symptoms of fever and leukopenia, who should be admitted for hematopoietic stem cell transplantation after remission by chemotherapy. In the course of chemotherapy, DSA was generated due to platelet transfusion, and had HLA gene loci incompatible with the donor of the first transplant, leading to the failure of the first transplant. The patient received platelet transfusion for several times before and after transplantation, and the results showed that the effective rate of MASPAT matched platelet transfusion was only 35.3%. Further analysis showed that the reason for the ineffective platelet transfusion was due to the missed detection of antibodies by MASPAT method. During the second hematopoietic stem cell transplantation, the DSA-negative donor was selected, and the matching platelets but ineffective transfusion during the primary transplantation were avoided. Finally, the patient was successfully transplanted and discharged from hospital.@*CONCLUSIONS@#DSA can cause graft failure or render the graft ineffective. For the platelet transfusion of patients with DSA, the platelet transfusion strategy with matching type only using MASPAT method will miss the detection of antibodies, resulting in invalid platelet transfusion.