Clinical Distribution,Serotypes and Drug Resistance Analysis of 425 Cases of Invasive Pneumococcal Disease Infectious in Children / 现代检验医学杂志

Objective To analyze the infection distribution,serotypes,and drug resistance of invasive pneumococcal disease(IPD)in children,and provide a reference for the standardized treatment of IPD and the rational use of antibiotics in clinical practice.Methods A total of 425 children with definitive diagnoses of IPD in the Department of Pediatrics,the Affiliated Suzhou Hospital of Nanjing Medical University between March 2019 and November 2022 were selected as the research subjects.Information from the medical records of these children was reviewed,clinical data was collected,serotyping by podoconiosis test on the specimens of Streptococcus pneumoniae strains sent for preservation was determined,and the susceptibility test was performed.Results A sum of 425 children with IPD(with a mean age of 2.16±0.93)were collected in this study.Analysis of clinical infection types showed 189 cases(44.47%)of bacteremia pneumonia,80 cases(18.82%)of simple bloodstream infection,76 cases(17.88%)of septic meningitis,11 cases(2.59%)of infectious pleurisy,9 cases(2.12%)of infective peritonitis,7 cases(1.65%)of bone and joint infection,7 cases(1.65%)of infective endocarditis,and 46 cases(10.82%)of other infections in combination.A total of 14 serotypes were confirmed in this study,with detection rates of 162 cases(38.12%),90 cases(21.18%),42cases(9.88%),38 cases(8.94%),14 cases(3.29%)and 8 cases(1.88%)for serotypes 19F,19A,14,23F,6A,and 6B,respectively.The susceptibility test indicated that the resistance rates of erythromycin and clindamycin were both high,with 95.53%(406/425)and 99.53(423/425),respectively,while the resistance rates of amoxicillin,cefepime,and cefotaxime were all relatively low,with 13.65%(58/425),9.06%(81/425),and 17.18%(73/425),respectively.Comparison between the two groups of cerebrospinal fluid(CSF)isolates and non-CSF isolates showed that the rates of resistance to penicillin were 69.74%and 24.07%(χ2=59.59,P＜0.05),the resistance rates to cefepime were 50.00%and 12.32%(χ2=57.44,P＜0.05),the resistance rates to meropenem were 40.79%and 29.23%(χ2=3.88,P＜0.05),respectively,with statistically significant differences.Conclusion Cultivation identification and drug resistance monitoring of IPD should be strengthened in clinical work.Antibiotics should be effectively used according to the drug susceptibility results to minimize the drug resistance of Streptococcus pneumoniae and improve the efficacy of drug therapy.

Research progress in prevention and cure of glucagon-like peptide-1 receptor agonists-1 receptor agonists for diabetic retinopathy / 中华眼底病杂志

Diabetic retinopathy (DR) is one of the most frequent complications of diabetes (T2DM), which is the main eye disease causing blindness in adults in recent years. At present, glucagon-like peptide-1 receptor agonists (GLP-1RA) have become the main drugs used in the treatment of diabetes due to its superior hypoglycemic, lipid-lowering, hypertensive and cardiovascular effects. A large number of studies have shown that GLP-1RA drugs can protect retinal microvascular and optic nerves in the treatment of diabetes through various ways, but some studies have found that GLP-1RA drugs represented by semaglutide may lead to the progress of DR. Therefore, GLP-1RA should be used cautiously for patients who with severe non-proliferative DR or proliferative DR. Regardless of whether T2DM patients are complicated with DR, the fundus retinal condition should be monitored regularly after the use of GLP-1RA drugs, and timely countermeasures should be taken when DR occurs and develops. The benefits of GLP-1RA used by diabetes patients are obvious to all, and scientific and rational drug use can prevent the occurrence and progress of DR, which can better benefit DR Patients.

Improvement effect of Phellodendron amurense polysaccharides on gouty nephropathy in rats and its mechanism / 中国药房

OBJECTIVE To study the effects of Phellodendron amurense polysaccharides （PAP） on improving gouty nephropathy （GN） in rats， and to investigate its mechanism primarily by interfering the p38 mitogen-activated protein kinase （p38 MAPK）/nuclear factor-κB（NF-κB）/tumor necrosis factor-α（TNF-α）. METHODS Sixty rats were randomly divided into normal group （water）， model group （water）， allopurinol group （positive control， 20 mg/kg）， PAP high-dose， medium-dose and low-dose groups （100， 50， 25 mg/kg， by raw material） after being stratified by body weight， with 10 rats in each group. Except for the normal group， the other groups were induced to construct GN model by giving 1 500 mg/kg potassium oxazinate and 100 mg/kg adenine intragastrically for 14 days. After modeling， the rats in each group were given relevant medicine/water intragastrically， once a day， for consecutive 28 days. After the last medication， the levels of biochemical parameters related to renal function [uric acid， creatinine （Cr）， blood urea nitrogen （BUN）， xanthine oxidase （XOD）] were detected in rats， and the histopathological changes in the rat kidney were observed. The protein expressions of monocyte chemoattractant protein-1（MCP-1），TNF-α and interleukin-6（IL-6） as well as the phosphorylation levels of p38 MAPK and NF-κB p65 protein were determined in renal tissue of rats. RESULTS Compared with the normal group， the model group suffered from the dilatation of renal tubules， structural damage to glomeruli， accompanied by inflammatory infiltration and fibrosis； the contents of uric acid， Cr， BUN and XOD， the protein expressions of MCP-1，TNF-α and IL-6 and the phosphorylation levels of p38 MAPK and NF-κB p65 protein were all increased significantly （P＜0.05 or P＜0.01）. Compared with the model group， the pathological symptoms of renal tissue in rats had been improved to varying degrees in different dose groups of PAP； the contents of uric acid， Cr， BUN and XOD， protein expressions of MCP-1， TNF-α and IL-6， the phosphorylation levels of p38 MAPK and NF-κB p65 protein in PAP high-dose and PAP medium-dose groups were all decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS PAP exhibits an anti-GN effect， the mechanism of which may be associated with inhibiting the p38 MAPK/NF-κB/TNF-α signaling pathway.

Self-reported quality of life in patients with coronary heart disease and analysis of the associated factors / 中华内科杂志

Objective: To investigate the quality of life and associated factors in patients with coronary heart disease (CHD) in China. Methods: A cross-sectional study of 25 provinces and cities in China was performed from June to September 2020. A questionnaire was used to collect the socio-demographic and clinical information of patients with CHD, while the European Five-dimensional Quality of Life Scale (EQ-5D) was used to assess the quality of life. Multiple linear regression model was performed to analyze the associated factors. Results: The median age of the 1 075 responders was 60 (52, 67) years, and 797 (74.1%) were men. The EQ-5D and EQ-VAS indices were 0.7 (0.5, 0.8) and 60.0 (40.0, 80.0). Among the five dimensions in the quality of life scale, the frequency of anxiety/depression was the highest (59.8%), while problems in self-care was the lowest (35.8%). In the multiple linear regression model, female, increasing age, obesity, comorbidity(ies), anxiety/depression, social media channels, and receiving the CABG therapy were associated with the lower EQ-5D index (all P<0.05). In addition, increasing age, obesity, comorbidity (ies), depression, anxiety and depression, social media channels, and receiving the CABG therapy were associated with lower EQ-VAS index (all P<0.05). Conclusion: Over half of the patients with CHD in China have a low quality of life, which is related to gender, age, obesity, treatment pathway, the presence or absence of comorbidity (ies), and psychological state. In addition to managing the adverse effects of traditional socio-demographic factors on the quality of life, clinical practices should pay attention to the psychological state of patients. Moreover, establishing a WeChat group for doctor-patient communication could improve the quality of life of CHD patients.

AI Cytomorphology Combined with DNA-image Cytometry for Identifying Benign and Malignant Pleural Effusion and Ascites / 肿瘤防治研究

Objective To explore the diagnostic value of artificial intelligence (AI) cytology combined with DNA-image cytometry (DNA-ICM) auxiliary diagnostic system for the identification of benign and malignant pleural effusion and ascites. Methods Liquid-based cytology technology (LCT), DNA-ICM, AI, and AI combined with DNA-ICM were used to identify benign and malignant pleural effusion and ascites specimens in 360 cases, and their sensitivity, specificity, accuracy, Kappa value, Youden index and AUC were statistically analyzed. Results The sensitivity, specificity, and accuracy of AI combined with DNA-ICM in detecting benign and malignant pleural effusion and ascites were 95.23%, 94.12%, and 94.44%, respectively, which were higher than those of the three other separate detection methods (all P < 0.05). The kappa values of LCT, DNA-ICM, and AI were 0.646, 0.642, and 0.586; their Youden index values were 0.693, 0.687, and 0.676, and their AUC values were 0.846, 0.843, and 0.838, respectively. The Kappa value of AI combined with DNA-ICM was 0.869, the Youden index was 0.893, and AUC was 0.947, which were all higher than those of the three detection methods alone. Conclusion Among the three separate detection methods, LCT has the highest reliability, authenticity, and diagnostic value, and it can be used as a common method for the clinical identification of benign and malignant pleural effusion and ascites. The diagnostic performance of AI combined with DNA-ICM auxiliary diagnosis system in identifying benign and malignant pleural effusion and ascites is better than those of the three separate detection methods and can be used as a reliable method for the clinical identification of benign and malignant pleural effusion and ascites.

Abnormal Prefrontal Brain Activation During a Verbal Fluency Task in Treatment-Resistant Depression Using Near-Infrared Spectroscopy

Objective@#The study investigated cognitive performance and brain function between treatment-resistant depression (TRD) and non- TRD patients to find potential neurobiological markers associated with refractoriness in depression patients. @*Methods@#Fourteen TRD patients, 26 non-TRD patients and 23 healthy controls (HC) were included in the present study. The neural function of prefrontal cortex (PFC) and cognitive performance among the three group were examined using near-infrared spectroscopy (NIRS) during verbal fluency task (VFT). @*Results@#Both TRD and non-TRD groups exhibited significantly worse VFT performance and lower activation of oxygenated hemoglobin (oxy-Hb) changes in the bilateral dorsolateral PFC (DLPFC) compared to the HC group. Within the TRD and non-TRD groups, VFT performance was no significant difference, but activation of oxy-Hb changes in dorsomedial PFC (DMPFC) in TRD patients was significantly lower than non-TRD patients. In addition, activation of oxy-Hb changes in right DLPFC were negatively correlated with the severity of depressive symptoms in depression patients. @*Conclusion@#Both TRD patients and non-TRD patients exhibited lower oxy-Hb activation in DLPFC. TRD patients exhibit lower oxy- Hb activation in DMPFC than non-TRD patients. fNIRS maybe a useful tool for predict depressive patients with or without treatment resistant.

Analysis of genetic variants and clinical manifestations of two children with Kabuki syndrome / 中华医学遗传学杂志

OBJECTIVE@#To report on two children with Kabuki syndrome due to variants of the KMT2D gene and summarize their clinical and genetic characteristics.@*METHODS@#Two children who had presented at the Ningbo Women and Children's Hospital respectively on August 19 and November 10, 2021 were selected as the study subjects. Clinical data were collected. Both children were subjected to whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing.@*RESULTS@#Both children had featured motor and language developmental delay, facial dysmorphism and mental retardation. Genetic testing revealed that both had harbored de novo heterozygous variants of the KMT2D gene, namely c.10205del (p.Leu3402Argfs*3) and c.5104C>T (p.Arg1702*), both of which were rated as pathogenic variants based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).@*CONCLUSION@#The c.10205del (p.Leu3402Argfs*3) and c.5104C>T (p.Arg1702*) variants of the KMT2D gene probably underlay the pathogenesis in these two children. Above finding has not only provided a basis for their diagnosis and genetic counseling, but also enriched the spectrum of KMT2D gene variants.

Role of the Voltage-Gated Proton Channel Hv1 in Nervous Systems / 神经科学通报·英文版

Hv1 is the only voltage-gated proton-selective channel in mammalian cells. It contains a conserved voltage-sensor domain, shared by a large class of voltage-gated ion channels, but lacks a pore domain. Its primary role is to extrude protons from the cytoplasm upon pH reduction and membrane depolarization. The best-known function of Hv1 is the regulation of cytosolic pH and the nicotinamide adenine dinucleotide phosphate oxidase-dependent production of reactive oxygen species. Accumulating evidence indicates that Hv1 is expressed in nervous systems, in addition to immune cells and others. Here, we summarize the molecular properties, distribution, and physiological functions of Hv1 in the peripheral and central nervous systems. We describe the recently discovered functions of Hv1 in various neurological diseases, including brain or spinal cord injury, ischemic stroke, demyelinating diseases, and pain. We also summarize the current advances in the discovery and application of Hv1-targeted small molecules in neurological diseases. Finally, we discuss the current limitations of our understanding of Hv1 and suggest future research directions.

Influencing factors of coronary heart disease in advanced aged population and therapeutic effect of PCI / 心血管康复医学杂志

Objective:To analyze influencing factors of coronary heart disease(CHD)in advanced aged population and the therapeutic effect of percutaneous coronary intervention(PCI).Methods:According to diagnosed as CHD or not,a total of 209 aged patients underwent cardio-and cerebrovascular examination in our hospital were divided into CHD group(n=104)and no CHD group(n=105),and general clinical data were compared between two groups.According to treatment method,CHD group was divided into routine treatment group(received routine medication)and PCI group;and recovery time,hospital stay,incidence rate of adverse events during admission and prognosis within one-year follow-up were compared between two groups.Influencing factors of CHD in aged population was analyzed.Results:Compared with no CHD group,there were significant rise in percentages of age＞80 years,smoking,diabetes mellitus,hypertension,total cholesterol＞5.17mmol/L,triglyceride＞1.7mmol/L,high density lipoprotein cholesterol(HDL-C)＜0.96mmol/L,low density lipoprotein cholesterol＞3.37mmol/L,uric acid＞420μmol/L and fibrinogen＞4 g/L in CHD group(P＜0.05 or＜0.01).Compared with routine treat-ment group,there were significant reductions in recovery time,hospital stay,incidence rates of adverse events,lu-men loss/restenosis,primary and secondary endpoint events within one-year follow-up in PCI group(P＜0.05 or＜0.01).Binary Logistic regression analysis indicated that age＞80 years,uric acid＞420μmol/L and HDL-C＜0.96mmol/L were independent risk factors for CHD in advanced aged population(OR=1.755～6.103,P＜0.05 or＜0.01).Conclusion:Age＞80 years,uric acid＞420μmol/L and HDL-C＜0.96 mmol/L are independent risk fac-tors for coronary heart disease in advanced aged population.PCI can significantly shorten recovery time and treat-ment time in advanced aged patients with coronary heart disease with good safety.

Mechanism of isovitexin in alcoholic fatty liver based on metabolomics combined with molecular docking analysis / 中国药理学通报

Aim To explore the effects of isovitexin (IVT) on alcoholic fatty liver disease (AFLD) and its mechanism based on metabolomics and in vivo methods and combined molecular docking. Methods 8-week-old male C57BL/6J mice were randomly divided into control, model and IVT groups, with 6 mice in each group. The control group was fed with alcoholic liquid feed control feed, the model group and IVT group were fed with alcoholic liquid feed model feed, and the IVT group was fed daily gastric IVT (100 mg • kg

Effect of Sea Cucumber Enzymolysis Fermentation Liquid on immunosuppressed mice based on metabonomics / 中国药理学通报

Aim To prepare the sea cucumber enzy¬molysis fermentation liquid (SCEFL) by enzymatic hydrolysis of protease and fermentation of probiotics and to investigate the effect of SCEFL on the immunosup-pression induced by cyclophosphamide in mice and to explore its mechanism by metabomic method. Methods The immunosuppressive model was induced by in-traperitoneal injection of cyclophosphamide. C57BL/6J mice were randomly divided into normal group, model group, Levamisole group, SCEFL groups (at low, medium and high doses). The pathological changes of spleen were observed by HE staining. The proportion of CD4

Toxoplasma gondii infection induces cell apoptosis via multiple pathways revealed by transcriptome analysis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Toxoplasma gondii is a worldwide parasite that can infect almost all kinds of mammals and cause fatal toxoplasmosis in immunocompromised patients. Apoptosis is one of the principal strategies of host cells to clear pathogens and maintain organismal homeostasis, but the mechanism of cell apoptosis induced by T. gondii remains obscure. To explore the apoptosis influenced by T. gondii, Vero cells infected or uninfected with the parasite were subjected to apoptosis detection and subsequent dual RNA sequencing (RNA-seq). Using high-throughput Illumina sequencing and bioinformatics analysis, we found that pro-apoptosis genes such as DNA damage-inducible transcript 3 (DDIT3), growth arrest and DNA damage-inducible α (GADD45A), caspase-3 (CASP3), and high-temperature requirement protease A2 (HtrA2) were upregulated, and anti-apoptosis genes such as poly(adenosine diphosphate (ADP)-ribose) polymerase family member 3 (PARP3), B-cell lymphoma 2 (Bcl-2), and baculoviral inhibitor of apoptosis protein (IAP) repeat containing 5 (BIRC5) were downregulated. Besides, tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1), TRAF2, TNF receptor superfamily member 10b (TNFRSF10b), disabled homolog 2 (DAB2)‍-interacting protein (DAB2IP), and inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) were enriched in the upstream of TNF, TNF-related apoptosis-inducing ligand (TRAIL), and endoplasmic reticulum (ER) stress pathways, and TRAIL-receptor 2 (TRAIL-R2) was regarded as an important membrane receptor influenced by T. gondii that had not been previously considered. In conclusion, the T. gondii RH strain could promote and mediate apoptosis through multiple pathways mentioned above in Vero cells. Our findings improve the understanding of the T. gondii infection process through providing new insights into the related cellular apoptosis mechanisms.

Segmentation of core infarct in acute ischemic stroke in diffusion weighted imaging using cascaded VB-Net / 中华放射学杂志

Objective:To explore the detection and segmentation of ischemic core infarct volume of the acute stroke in diffusion weighted imaging (DWI) images using cascaded VB-Net.Methods:MRI data of 1 500 patients (2 456 lesions) with acute ischemic stroke in Henan Provincial People′s Hospital from December 2016 to December 2018 were retrospectively analyzed. Firstly, manual segmentation of ischemic core was performed on DWI images (b=1 000 s/mm 2), and then all data were divided into training set, validation set and independent test set by 8∶1∶1. Then, the cascaded VB-Net was constructed, and the core infarct was automatically detected and segmented in the test set. Interclass correlation coefficient (ICC) was used to evaluate the consistency of volume size measured by manual segmentation and cascaded VB-Net. The patients were divided into large ischemic core lesion group (ischemic core volume ≥10 ml) and small ischemic core lesion group (ischemic core volume<10 ml), and the Dice coefficient difference between the two groups was compared using Mann-Whitney U test. Results:In independent test set, cascaded model had the detection rate of 94.6% (243/257) with Dice coefficient of 0.76 (0.68, 0.84). The agreement of cacade VB-Net segmented [4.19(1.21,14.13)ml] and manual segmented ischemic core infarct volume [4.08(1.19,17.92)ml] was high (ICC=0.97, P<0.001). There was no significant difference in Dice coefficient between large and small lesion groups [0.76 (0.69, 0.85), 0.76 (0.67, 0.84), Z=-0.44, P=0.657]. Conclusions:The cascaded VB-Net model provided a tool to realize automatic detection, segmentation, and calculation of ischemic core infarct volume. It has good segmentation accuracy and high consistency with manual segmentation, which can provide an auxiliary decision-making tool for the selection of treatment plans.

Effect and Mechanism of Lily Polysaccharide Combined with Astragalus Polysaccharide on Depressive Behavior in Chronic Stress Mice / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of antidepressant effect of lily polysaccharide （LLP）and astragalus polysaccharide（APS）. MethodSixty KM mice were randomly divided into blank group， model group， fluoxetine hydrochloride （8 mg·kg-1）group， LLP （0.2 g·kg-1）group， APS （0.2 g·kg-1）group and polysaccharide combination （LLP+APS，0.1 g·kg-1+0.1 g·kg-1）group， with 10 mice in each group. Except the blank group， the other groups were given chronic unpredictable mild stress （CUMS） induced mouse depression model. On the 29th day of modeling，fluoxetine hydrochloride group was given corresponding dose of fluoxetine hydrochloride， and polysaccharide groups were given corresponding drug. The depressive behavior of mice was evaluated by behavioral indexes such as body mass change， open field test. The morphological changes of hippocampal CA1 neurons were observed by Nissl staining. The contents of 5-hydroxytryptamine （5-HT）， adrenocorticotropic hormone （ACTH）， and corticosterone （CORT）， in brain tissue and plasma were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression levels of related proteins in adenylate cyclase/cyclic adenylate phosphate/protein kinase A （AC/cAMP/PKA） signal pathway. ResultCompared with the blank group， mice in the model group gained weight slowly， the total distance， central distance and sugar water preference rate decreased significantly （P<0.01）， the depressive behavior was significant， the hippocampal neurons were seriously damaged， the content of 5-HT decreased （P<0.01）， the contents of ACTH and CORT increased significantly （P<0.01）， adenylate cyclase 6（ADCY6）， PKA and cAMP response element binding protein-1 （CREB-1） and brain-derived neurotrophic factor （BDNF） protein expression decreased significantly （P<0.01）. Compared with the model group， depressive behavior of mice in LLP group， APS group and LLP+APS group was significantly improved （P<0.01）. The antidepressant effect of LLP+APS was better than that of LLP and APS. Each administration group could alleviate the damage of hippocampal neurons in varying degrees， significantly increase the content of 5-HT in brain tissue （P<0.01）， and reduce the levels of ACTH and CORT in plasma （P<0.05）. The protein levels of ADCY6， PKA， CREB-1 and BDNF were significantly increased （P<0.05）. ConclusionThe antidepressant effect of LLP+APS is significantly enhanced and has a synergistic effect. The mechanism may be closely related to affecting the content of neurotransmitters， inhibiting HPA axis activity and activating AC/cAMP/PKA signal transduction pathway.

Mechanisms of catapol inhibiting differentiation and glycolysis of Thl7 cells through MiR-143-3p / 中国药理学通报

Aim To investigate the mechanism of eata- pol (CAT) inhibiting differentiation and glyeolysis of Thl7 eel Is through miR-143-3p.Method The peripheral hloorl CD4 ∗ T eells of HA patients were obtained to deteet the expression of miR-143-3p and the mRNA levels of key glycolytic enzymes, ineluding glucose transporter 1 ( Glutl ) , hexokinase 2 ( HK2 ) , pyruvate kinase 2 (PKM2) , laetate dehydrogenase A ( LDHA).The differentiation of Thl7 eells was induced in vitro, and the ShRNA/lentivirus was applied to achieve the overexpression or knockdown of miR- 143-3 p.Un-transfected eells were divided into control group and CAT group (20, 40, 80 mg • L 1 ) , and transfected eells were divided into four groups: negative control group, miR-143-3p inhibitor group, miR- 143-3p mimies group, miR-143-3p inhibitor + CAT group.The percentage of Thl7 eells was deteeted by flow cytometry, and the level of IL-17A was detected by EL1SA.Quantitative real-time PCR was used to detect the mRNA expression of miR-143-3p and key glycolytic enzymes, and the levels of pyruvate and lactate were also detected.Results The mRNA expression of miR-143-3p in RA peripheral blood CD4 ∗ T cells was negatively correlated with disease severity ( DAS28 ) , transcription factor ROR-yt, and the key glycolytic enzymes Glutl/HK2/LDHA.Compared with negative control group, the down-expression of miR-143-3p markedly elevated the mRNA expression of ROR-yt, Glutl, HK2, LDHA, and the levels of IL-17A, pyruvate, lactate.Catalpol groups significantly up-regula- ted the expression of miR-143-3p, decreased the mRNA expression of HK2/LDHA and the levels of pvru- vate/lactate, and inhibited Thl7 cells differentiation.Compared with miR - 1 4 3 - 3 p inhibitor group , catapol could significantly inhibit the abnormal up-regulated of HK2/LDHA mRNA relative expression, pyruvate/lactate levels and the abnormal differentiation of Thl7 eells.Conclusion MiR-143-3p inhibits the differentiation and glycolysis of Thl7 cells.Catalpol could sup-press the glycolysis and differentiation of Thl7 eells by regulating mill-143-3p.

Effects of neferine on invasion and migration of non-small cell lung cancer H1299 cells via inhibiting ROCK pathway / 中国药理学通报

Aim To observe the inhibitory effect of neferine(Nef)on the migration and invasion of non-small cell lung cancer(NSCLC)H1299 cells by blocking ROCK pathway.Methods H1299 cells were taken for in vitro culture, and treated with different concentrations of Nef.H1299 cell viability was measured by CCK-8 method to determine the dose of the experimental group.The migration and invasion abilities of H1299 cells were detected by cell scratch test and Transwell chamber test.The expression of matrix metalloproteinases MMP-2 and MMP-9 secreted from lung cancer cells was detected by enzyme linked immunosorbent assay(ELISA).The protein level of ROCK1 in H1299 cells was tested by real-time fluorescent quantitative PCR and Western blot; the binding mode and affinity between Nef and ROCK1 were stimulated by AutoDock semi flexible docking method.Results The doses of Nef in the experimental group were determined as 4, 6 and 10 μmol·L-1.These three concentrations of Nef could inhibit the migration and invasion of H1299 lung cancer cells to a certain degree in a dose-dependent manner.At the same time, Nef reduced the expression of MMP-2, MMP-9 and ROCK1 proteins related to the migration and invasion of the cancer cells.In addition, the affinity of Nef to ROCK1 was significantly higher than that of fasudil, an inhibitor of ROCK, and the binding force was stronger to A-chain of ROCK1.Conclusions As a potential natural anticancer compound, Nef can inhibit the migration and invasion of NSCLC by reducing the expression of MMP-2, MMP-9 and ROCK1 proteins related to the migration and invasion of the cancer cells.

Role of microRNA-132 and Mecp2 in methamphetamine dependence / 中国药理学通报

Aim To explore the roles of miRNA-132 and its related proteins(Mecp2, CREB)in the mechanism of methamphetamine(MA)-induced neurotoxicity and dependence.Methods The rats were intraperitioneally injected(ip)with MA(10 mg·kg-1·d-1)to establish methamphetamine dependence model with different dependent time courses of 1 week, 2 weeks, and 4 weeks respectively.The miRNA-132 and Mecp2 mRNA were detected by RT-qPCR, and the Mecp2, p-Mecp2, CREB and p-CREB proteins were detected by Western blot in the tissues of frontal cortex and hippocampus.Results In the frontal cortex, the miRNA-132 and Mecp2 mRNA were up-regulated in MA-dependent groups(P<0.05 and P<0.01), while the Mecp2 protein were down-regulated(P<0.01).MA could promote the phosphorylation of Mecp2 protein in the frontal cortex(P<0.01).In hippocampus, the miRNA-132 was down-regulated in the MA-dependent groups, but Mecp2 mRNA was up-regulated(P<0.05).Mecp2 protein increased in MA-dependent 1 week group(P<0.05), and then recovered with the prolonged time of MA dependence, then decreased in MA-dependent 4 weeks groups(P<0.05)in hippocampus.The phosphorylation level of Mecp2 was significantly decreased in the 1 week group(P<0.01), and then increased in the 2 weeks group(P<0.01)in hippocampus.Conclusions MA could induce an abnormal expression of miRNA-132 in the frontal cortex and hippocampus, and miRNA-132 might inhibit the translation of Mecp2 mRNA and induce the decrease expression of Mecp2 protein in the frontal cortex.But in hippocampus, miRNA-132 does not show the correlation with the Mecp2 expression trend of the frontal cortex.And miRNA-132 regulation does not depend on the expression of Mecp2 in hippocampus.

Comparison on efficacy between fascia-oriented versus vascular-oriented lateral lymph node dissection in patients with rectal cancer / 中华胃肠外科杂志

Objective: To compare the postoperative function, the short-term and long-term outcomes between fascia-oriented and vascular-oriented lateral lymph node dissection (LLND) in patients with rectal cancer. Methods: A retrospective cohort study was performed. Clinical data of patients who received total mesorectal excision (TME) with LLND at National Cancer Center, Cancer Hospital of Chinese Academy of Medical Science from January 2014 to December 2019 were retrospectively collected. Inclusion criteria were as follows: (1) rectal cancer was pathologically diagnosed, and the lower margin was below the peritoneal reflection. (2) resectable advanced rectal cancer with suspected lateral lymph node metastasis was evaluated based on rectal MRI assessment. (3) preoperative MRI showed lateral lymph node short diameter ≥5 mm and/or lymph node morphology (spike, blur, irregular) as well as heterogenous signal intensity. Lymph node shrinkage was less than 60% after receiving neoadjuvant therapy based on the reassessment of rectal MRI. (4) TME+LLND surgery was performed synchronously. Exclusion criteria were as follows: (1) previous history of pelvic surgery; (2) preoperative cystitis, urethritis, moderate and severe prostatic hyperplasia and other diseases resulting in abnormal urination function; (3) preoperative sexual dysfunction or loss of function; (4) patients receiving LLND due to lateral recurrence after TME; (5) distant metastasis of the tumor at initial diagnosis; (6) Incomplete collection of clinical data. A total of 73 consecutive patients were enrolled in this study. Based on the surgical approaches in performing LLND, patients were divided into fascia-oriented group (n=30) and vascular-oriented group (n=43). There were no significant differences in baseline data between the two groups (all P>0.05). The main outcome indicators of this study were the incidence of postoperative urinary and male sexual dysfunction, the efficacy, the number of lateral lymph nodes harvested and the detection rate of positive lymph nodes. Overall survival (OS) rates and progression free survival (PFS) rates were calculated by the Kaplan-Meier method and compared by log-rank test. Results: All patients in both groups completed surgery successfully. There were no significant differences in operation time, intraoperative blood loss, postoperative complications, and the length of hospital stay between the two groups (all P>0.05). In the whole group, the incidence of postoperative urinary dysfunction and male sexual dysfunction was 43.8% (32/73) and 62.5% (25/40), respectively. The median number of lateral lymph nodes harvested was 8.0(4.0,11.0) with a positive rate of 20.5%(15/73). Compared to the vascular-oriented group, the fascia-oriented group demonstrated a decreased rate of urinary dysfunction [26.7% (8/30) vs. 55.8% (24/43), χ(2)=6.098, P=0.014], lower rate of sexual dysfunction in males [6/15 vs. 76% (19/25), χ(2)=5.184, P=0.023], more harvested lateral lymph nodes [M (P25, P75): 9.5 (6.8, 15.3) vs. 6.0 (3.0, 9.0), Z=-2.849, P=0.004]. There was no significant difference in the positvie rate of lateral lymph nodes between the two groups [20% (6/30) versus 20.9% (9/43), χ(2)=0.009, P=0.923]. Three(4.1%) patients were lost during a median follow-up of 34 (1-66) months. The 3-year PFS and OS of the whole cohort were 69.5% and 88.3%, respectively. No significant difference in 3-year PFS rates (79.6% vs. 62.0%, P=0.172) and 3-year OS rates (91.2% vs. 85.9%, P=0.333) were observed between the fascia-oriented group and the vascular-oriented group (both P>0.05). Conclusion: Fascia-oriented LLND is associated with lower risk of postoperative urinary and male sexual dysfunction in patients with rectal carcinoma, and harvest of more lymph nodes, but no significant advantage in long-term survival.

Effects of sinapine thiocyanate on cutaneous squamous cell carcinoma and its related mechanism / 中国药理学通报

Aim To investigate the effects of sinapine thiocyanate (ST) on the malignant biological behavior of cutaneous squamous cell carcinoma A431 and Colo-16 cells, and its mechanism. Methods The fibroblast cells were treated with 20 μmol · L

Current Situation of Methamphetamine Abuse and Related Research Progress / 法医学杂志

Drug problem is a major social and public security problem in the world. Drug abuse poses a great threat to economic development, social stability and public health. In recent years, synthetic drugs represented by methamphetamine have surpassed traditional drugs such as morphine, heroin, ketamine and become one of the most abused drugs in the world. In order to solve the problem of drug abuse, it is of great theoretical value and practical significance to carry out all-round and multi-level scientific research on drug-related issues. Based on the current situation of drug abuse, this article reviews research progresses on the epidemiology of methamphetamine abuse, the monitoring technology, the basic researches on toxicity damage, the withdrawal drug screening, the related clinical comorbidity and the testing technologies, comprehensively presenting the development trend of methamphetamine abuse related issues.