Radiomic Analysis Based on Gd-EOB-DTPA Enhanced MRI for the Preoperative Prediction of Ki-67 Expression in Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: To develop and validate a random forest model based on radiomic features in Gd-EOB-DTPA enhanced MRI for predicting the Ki-67 expression in solitary HCC. MATERIALS AND METHODS: This retrospective study analyzed 258 patients with solitary HCC. Significant clinicoradiological factors were identified through univariate and multivariate analyses for distinguishing HCC with high (>20%) and low (≤20%) Ki-67 expression. Radiomic features were extracted at Gd-EOB-DTPA enhanced MRI. The recursive feature elimination (RFE) strategy was employed to screen robust radiomic features, and the Random Forest (RF) algorithm was utilized to rank radiomic features and construct prediction models. The AUC, accuracy, precision, recall, and f1-score were used to evaluate the performance of RF models. RESULTS: Multivariate analysis identified serum AFP level, tumor size, growth type, and peritumoral enhancement as independent predictors for HCC with high Ki-67 expression. The clinicoradiological-radiomic model that incorporated the clinicoradiological predictors and the top ten radiomic features outperformed the clinicoradiological model in the training set (AUCs 0.876 vs. 0.780; p < 0.001), though the test set did not have a statistical significance (AUCs 0.809 vs. 0.723; p = 0.123). The addition of clinicoradiological predictors did not yield a significant improvement in the performance of radiomic features in both sets (training, p = 0.692; test, p = 0.229). Decision curve analysis further confirmed the clinical utility of the RF models. CONCLUSION: The RF models based on radiomic features of Gd-EOB-DTPA enhanced MRI achieved satisfactory performance in preoperatively predicting Ki-67 expression in HCC.

Application of Data Mining Technology in the Screening for Gallbladder Stones: A Cross-Sectional Retrospective Study of Chinese Adults

Purpose@#The purpose of this study was to use data mining methods to establish a simple and reliable predictive model based on the risk factors related to gallbladder stones (GS) to assist in their diagnosis and reduce medical costs. @*Materials and Methods@#This was a retrospective cross-sectional study. A total of 4215 participants underwent annual health examinations between January 2019 and December 2019 at the Physical Examination Center of Shengjing Hospital Affiliated to China Medical University. After rigorous data screening, the records of 2105 medical examiners were included for the construction of J48, multilayer perceptron (MLP), Bayes Net, and Naïve Bayes algorithms. A ten-fold cross-validation method was used to verify the recognition model and determine the best classification algorithm for GS. @*Results@#The performance of these models was evaluated using metrics of accuracy, precision, recall, F-measure, and area under the receiver operating characteristic curve. Comparison of the F-measure for each algorithm revealed that the F-measure values for MLP and J48 (0.867 and 0.858, respectively) were not statistically significantly different (p>0.05), although they were significantly higher than the F-measure values for Bayes Net and Naïve Bayes (0.824 and 0.831, respectively; p<0.05). @*Conclusion@#The results of this study showed that MLP and J48 algorithms are effective at screening individuals for the risk of GS.The key attributes of data mining can further promote the prevention of GS through targeted community intervention, improve the outcome of GS, and reduce the burden on the medical system.

Analysis of gene characteristics and core genome characteristics of carbapenem-resistant Enterobacter cloacae in rural residents of Weifang City, Shandong Province / 中华预防医学杂志

Objective: To investigate the drug-resistant gene characteristics and core genome characteristics of carbapenem-resistant Enterobacter cloacae (CR-ECL) in rural residents of Weifang City, Shandong Province. Methods: Fecal samples were collected from rural community residents in Weifang City, Shandong Province in 2017. Drug-resistant strains were screened using a carbapenem-resistant enterobacter chromogenic medium. CR-ECL positive strains were acquired via Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry(MALDI-TOFMS) analysis. The antibiotic resistance phenotype of CR-ECL was determined using a microbroth dilution assay. Whole genome sequencing (WGS) and analysis were conducted, along with an examination of the immediate vicinity of the blaNDM gene and phylogenetic analysis of the strains. Results: A total of 628 fecal samples were collected and tested, of which 6 were CR-ECL positive (detection rate 0.96%), all exhibiting multiple drug resistance (MDR) phenotypes. Six CR-ECL strains had four MLST genotypes (ST), all of which carried multiple drug resistance genes (blaNDM-1, blaNDM-5, etc.) and virulence genes (acrA, acrB, entB, fepC, etc.). There were mobile genetic elements ISAba125, TN3-IS3000, TN3 and IS5 in the genetic environment surrounding the blaNDM gene. The phylogenetic tree showed that the multi-locus sequence typing of the core genome (cgMLST) was consistent with the single nucleotide polymorphism (SNPs) results. The cgMLST results showed that the allele differences between strains 2BC0101B and 2BC0251B, 2BG0561B and 2BI0221B were 2 and 1, respectively. The SNPs results showed that the above two pairs of bacteria also clustered together. It was found that the strains of chicken fecal samples in the National Center for Biotechnology Information (NCBI) database were located in the center of the evolutionary tree, and the local sequences could be traced back to American human sequences. Conclusion: Multidrug-resistant CR-ECL is detected in rural community residents in Weifang City, Shandong Province.

Analysis of gene characteristics and core genome characteristics of carbapenem-resistant Enterobacter cloacae in rural residents of Weifang City, Shandong Province / 中华预防医学杂志

Objective: To investigate the drug-resistant gene characteristics and core genome characteristics of carbapenem-resistant Enterobacter cloacae (CR-ECL) in rural residents of Weifang City, Shandong Province. Methods: Fecal samples were collected from rural community residents in Weifang City, Shandong Province in 2017. Drug-resistant strains were screened using a carbapenem-resistant enterobacter chromogenic medium. CR-ECL positive strains were acquired via Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry(MALDI-TOFMS) analysis. The antibiotic resistance phenotype of CR-ECL was determined using a microbroth dilution assay. Whole genome sequencing (WGS) and analysis were conducted, along with an examination of the immediate vicinity of the blaNDM gene and phylogenetic analysis of the strains. Results: A total of 628 fecal samples were collected and tested, of which 6 were CR-ECL positive (detection rate 0.96%), all exhibiting multiple drug resistance (MDR) phenotypes. Six CR-ECL strains had four MLST genotypes (ST), all of which carried multiple drug resistance genes (blaNDM-1, blaNDM-5, etc.) and virulence genes (acrA, acrB, entB, fepC, etc.). There were mobile genetic elements ISAba125, TN3-IS3000, TN3 and IS5 in the genetic environment surrounding the blaNDM gene. The phylogenetic tree showed that the multi-locus sequence typing of the core genome (cgMLST) was consistent with the single nucleotide polymorphism (SNPs) results. The cgMLST results showed that the allele differences between strains 2BC0101B and 2BC0251B, 2BG0561B and 2BI0221B were 2 and 1, respectively. The SNPs results showed that the above two pairs of bacteria also clustered together. It was found that the strains of chicken fecal samples in the National Center for Biotechnology Information (NCBI) database were located in the center of the evolutionary tree, and the local sequences could be traced back to American human sequences. Conclusion: Multidrug-resistant CR-ECL is detected in rural community residents in Weifang City, Shandong Province.

Autosomal recessive axonal neuropathy with neuromyotonia in a Tibetan family caused by HINT1 gene variation and literature review / 中华实用儿科临床杂志

Objective:To summarize the characteristics of autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) caused by HINT1 gene mutation. Methods:Retrospective case summary.Clinical data of 2 Tibetan siblings diagnosed with ARAN-NM in the Department of Pediatrics of Peking University First Hospital in August 2023 were retrospectively analyzed.A review of literature reporting relevant Chinese patients was conducted.Results:The proband and her elder brother were aged 13 and 19, respectively.Both developed abnormal gait at the age of 11, followed by varus, claudication, and weak thumb strength.The proband also had neuromyotonia.Physical examinations showed that the proband and her elder brother had decreased muscle strength of the extremities, mainly in the thumbs and distal ends of lower limbs.The distal muscles of the proband′s lower extremities and the muscles of both hands of the proband′s elder brother were atrophied.Both feet showed talipes equinovarus in the proband and her elder brother.The proband′s electromyography (EMG) showed peripheral nerve injuries (motor and sensory axonal involvement, especially in distal ends) and myotonic potentials.The trio-whole exon sequencing detected homozygous pathogenic variation in HINT1 gene in both the proband and her elder brother, who were diagnosed as ARAN-NM based on c. 169A>G (p.K57E). After the Carbamazepine treatment, the proband′s neuromyotonia, numbness and weakness were relieved.Both the proband and her elder brother underwent orthopaedic surgery and rehabilitation.Their foot deformities and gait were significantly improved.Two Chinese literatures (2 patients) and four English literatures (8 patients) were retrieved.Including the proband and her elder brother in this study, there were 12 ARAN-NM patients, 10 of whom had clinical data.The ages of onset and diagnosis were 2-16 (1 case unknown) and 13-33 years old, respectively.Myasthenia was present in 9 patients, especially in distal ends.Eight patients were complicated with neuromyotonia, nine patients with muscle atrophy, seven patients with foot deformity, and two patients with sensory disturbance.Creatine kinase(CK) was elevated in all 9 patients tested or CK.EMG showed neurogenic injuries in all patients and neuromyotonia discharge in six patients.Three patients were treated with Carbamazepine, and some symptoms were relieved.Missense/nonsense mutations were found in the 12 patients, and the high-frequency variation was c. 112T>C (p.C38R). Conclusions:ARAN-NM is a rare autosomal recessive neuromuscular disease caused by HINT1 gene mutation.There is no ethnic difference in clinical manifestations, mainly distal limb weakness with neuromyotonia.Carbamazepine can alleviate some symptoms, and orthopaedic surgery can improve foot deformity and gait.

miR-20a regulates pressure overload-induced cardiac hypertrophy / 中国组织工程研究

BACKGROUND:Cardiac hypertrophy is an adaptive response of the heart to physiological and pathological stimuli such as pressure overload.It is of compensatory significance in the early stage,but if the stimulation continues,it can cause cardiomyopathy leading to heart failure.MicroRNAs are involved in the regulation of cardiac hypertrophy.However,the role of miR-20a in pressure overload-induced cardiac hypertrophy has not been reported. OBJECTIVE:To investigate the role of miR-20a in pressure overload-induced cardiac hypertrophy and the underlying mechanisms. METHODS:Transverse aortic constriction was used to induce cardiac hypertrophy in vivo and angiotensin Ⅱ was used to induce H9c2 cell models of cardiac hypertrophy in vitro.MiR-20a was overexpressed in vivo by intramyocardial injection of miR-20a overexpressing adenovirus and in vitro by transfecting miR-20a mimic into H9c2 cells.Cardiac hypertrophy was assessed by measuring heart weight/body weight ratio,cell surface area,and myocardial fibrosis.The expression levels of atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain and miR-20a were detected by real-time fluorescence quantitative PCR.Mitochondrial fission was detected by MitoTracker.The downstream target genes of miR-20a were predicted by RNAhybrid software. RESULTS AND CONCLUSION:(1)The expression level of miR-20a was significantly decreased in both hypertrophic cardiomyocytes and hearts(P<0.05).(2)At the animal level,overexpression of miR-20a significantly inhibited transverse aortic constriction-induced cardiac hypertrophy,including decreasing the upregulated expression level of hypertrophic marker genes(P<0.05),reduced the enlarged heart volume,reducing the increased heart weight/body weight ratio(P<0.01),reducing the increased myocardial cross-sectional area(P<0.05),and attenuating fibrosis(P<0.01).(3)At the cellular level,overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced cardiomyocyte hypertrophy,including decreasing the upregulated expression levels of atrial natriuretic peptide(P<0.05),brain natriuretic peptide(P<0.01)and β-myosin heavy chain(P<0.05),reducing the increased protein/DNA ratio(P<0.01),and suppressing the increased cell surface area(P<0.05).(4)Overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced mitochondrial fission(P<0.05).(5)The results of RNAhybrid software analysis showed that miR-20a and the mRNA 3'untranslated region of cAMP-dependent protein kinase inhibitor alpha were well complementary and the predicted binding sites were highly conserved.(6)In conclusion,miR-20a is significantly down-regulated in pressure overload-induced cardiac hypertrophy.Overexpression of miR-20a inhibits cardiac hypertrophy at both the cellular level and animal level and attenuates angiotensin Ⅱ-induced mitochondrial fission.

Evaluation of 256 slice spiral CTA of coronary and serum indicators on the severity of coronary artery stenosis of patients with coronary heart disease / 中国医学装备

Objective:To explore the evaluation of 256 slice spiral computed tomography angiography(CTA)of coronary,serum lipoprotein associated phospholipase A2(Lp-PLA2)and angiopoietin like protein 3(ANGPTL3)on the severity of coronary artery stenosis of patients with coronary heart disease.Methods:A total of 102 patients with coronary heart disease who were diagnosed and treated at Hebei Chest Hospital from July 2022 to March 2023 were selected as the study subjects.According to the Gensini score about the severity of coronary artery stenosis,they were divided into mild stenosis group(0 score≤Gensini score≤20 scores),moderate stenosis group(20 scores<Gensini score≤60 scores)and severe stenosis group(Gensini score>60 scores),with 34 cases in each group.The minimum lumen diameter(MLD),percentage of area of stenosis(%AS),percentage of diameter of stenosis(%DS),minimum lumen area(MLA),Lp-PLA2 and ANGPTL3 among three groups were compared.The diagnostic efficiency of the severity of coronary artery stenosis was predicted according to receiver operating characteristic(ROC)curve.Results:The MLA and MLD values in severe stenosis group were significantly lower than those in moderate and mild stenosis groups,while%AS and%DS were significantly higher than those in moderate and mild stenosis groups(t=6.905,4.083,5.871,6.976,3.387,2.198,2.668,3.505,P<0.05),respectively.The Lp-PLA2 and ANGPTL3 values in severe stenosis group were significantly higher than those in moderate and mild stenosis groups(t=4.164,8.220,2.575,3.050,P<0.05),respectively.ROC curve analysis showed that the area under curve(AUC)values of MLA,MLD,%AS,%DS,CCTA comprehensive parameter,LpPLA2 and ANGPTL3 were respectively were 0.838,0.690,0.742,0.801,0.904,0.808 and 0.807 in predicting the severity of coronary artery stenosis.The sensitivities of them were respectively 91.20%,91.20%,64.70%,94.10%,97.10%,70.60%and 88.20%.The specificities of them were respectively 76.50%,57.40%,75.00%,50.00%,70.60%,97.10%and 70.60%.The AUC value of CCTA comprehensive parameter was respectively higher than that of LpPLA2 and ANGPTL3,but the difference was not statistically significant(P>0.05).Conclusion:256 slice spiral CCTA,serum Lp-PLA2 and ANGPTL3 have a certain efficiency in assessing the severity of coronary artery stenosis of coronary heart disease,and 256 slice spiral CCTA has higher predictive efficiency.

Research progress on issues concerning the definition of cognitive frailty / 中华老年医学杂志

Since the first operational definition of cognitive frailty was proposed by the expert consensus group of the International Academy of Nutrition and Aging and the International Association of Gerontology and Geriatrics in 2013, frailty and neurocognitive assessment has become the standard diagnostic tool.Since then, the reported prevalence in the literature for cognitive frailty in community-dwelling elderly people vary by dozens of times, as a result of different scales and diagnostic cut-off points, seriously affecting health decision-making.This article reviewed the current literature with a focus on the re-recognition of the clinical significance of cognitive frailty, the limitations of existing assessment tools for diagnosis, and possible solutions in the future.

Analysis of Ethical Cognition and Training Needs of Medical Researchers in China / 中国医学伦理学

The cognition and attitude of scientific research ethics consciousness affect the willingness and degree of individual researchers to follow research ethics norms. This study investigated the awareness, access and training needs of Chinese medical researchers (n=11 164) on the knowledge of scientific research ethics. The survey found that more than 50.0% of people were aware of the "golden rice incident" and "skull transplantation"; 80.0% of people were knew of Operational Quideline for the Ethic Review of Biomedical Research Involving Human Subject; 90.0% said that "respecting people" and "not harming" were the basic ethical principles, but 42.8% and 75.1% chose "beneficial" and "fair" respectively; more than 60.0% of people have acquired scientific research ethics knowledge through "self-study", "special training organized by units" or "words and deeds taught by mentors or colleagues", but still 30.0% have not participated in scientific research ethics lectures in recent three years; In terms of training needs, more than 50.0% chose "ethical norms for research and application", followed by "frontier ethical issues" (41.0%) and "ethical review" (36.7%). Based on this, this paper puts forward some suggestions to improve the content and form of scientific research ethics education and training in China.

Identification and expression analysis of TCP family members in tobacco (Nicotiana tabacum L.) / 生物工程学报

TCP family as plant specific transcription factor, plays an important role in different aspects of plant development. In order to screen TCP family members in tobacco, the homologous sequences of tobacco and Arabidopsis TCP family were identified by genome-wide homologous alignment. The physicochemical properties, phylogenetic relationships and cis-acting elements were analyzed by bioinformatics. The homologous genes of AtTCP3/AtTCP4 were screened, and RT-qPCR was used to detect the changes of gene expression upon 20% PEG6000 treatment. The results show that tobacco contains 63 TCP family members. Their amino acid sequence length ranged from 89 aa to 596 aa, and their protein hydropathicity grand average of hydropathicity (GRAVY) ranged from -1.147 to 0.125. The isoelectric point (pI) ranges from 4.42 to 9.94, the number of introns is 0 to 3, and the subcellular location is all located in the nucleus. The results of conserved domain and phylogenetic relationship analysis showed that the tobacco TCP family can be divided into PCF, CIN and CYC/TB1 subfamilies, and each subfamily has a stable sequence. The results of cis-acting elements in gene promoter region showed that TCP family genes contain low docile acting elements (LTR) and a variety of stress and metabolic regulation related elements (MYB, MYC). Analysis of gene expression patterns showed that AtTCP3/AtTCP4 homologous genes (NtTCP6, NtTCP28, NtTCP30, NtTCP33, NtTCP42, NtTCP57, NtTCP63) accounted for 20% PEG6000 treatment significantly up-regulated/down-regulated expression, and NtTCP30 and NtTCP57 genes were selected as candidate genes in response to drought. The results of this study analyzed the TCP family in the tobacco genome and provided candidate genes for the study of drought-resistance gene function and variety breeding in tobacco.

International students' collective resilience in crisis: Sense of community reduced anxiety via social contact and social support during lockdown.

Objectives: The role of community in individuals' well-being has been extensively examined in the Western context. However, little is known about how the host community is related to sojourners' well-being in a crisis in an Asian context. The current study aims at exploring international students' sense of community in the Chinese context under the direct threat of a global health crisis. Methods: Using a cross-sectional sample of 102 international students staying in Wuhan during the 76-day lockdown at the earliest stage of the COVID-19 pandemic, the current study explored the relationship between international students' sense of community and anxiety, and the mediating role of social contact, social support from three key sources in the host community (host university, international students, and Chinese friends). Results: Results showed that participants' stronger sense of community indirectly reduced anxiety via the role of sources of contact and support from the host community. Conclusions: This study provided further evidence to support the nurturance of the sense of community in community resilience and provided implications on how the host community can help to enhance sojourners' psychological well-being in a global crisis.

Mare's milk attenuates sodium dextran sulfate induced inflammation in mouse ulcerative colitis / 细胞与分子免疫学杂志

Objective To investigate the immunomodulatory effect of mare's milk on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. Methods Kunming mice were randomly divided into a blank group(0.8 mL/day saline by gavage) and a DSS modeling group. After modeling, the DSS modeling group was further divided into a control group (0.8 mL/day saline), a salazosulfapyridine (SASP) treated group(430 mg/(kg.d)) and a mare's milk group(0.8 mL/day), with 16 mice in each group. After 10 days of gavage administration, HE staining was performed to observe colonic inflammation, and the disease activity index (DAI) and colonic mucosal damage index (CMDI) were scored. ELISA was used to determine the levels of interleukin 1β (IL-1β), IL-6, and IL-10 in mouse colonic tissues, and flow cytometry was used to detect the percentages of CD4+ and CD8+ T lymphocytes in peripheral blood. Results Compared to the blank group, all indexes in mice of the control group indicated that DSS successfully induced UC. Compared to the control group, colon shortening in UC mice was attenuated in the mare's milk group; inflammation and ulcer formation in colonic tissues were inhibited; DAI and CMDI scores were lowere; IL-1β and IL-6 levels in mouse colonic tissues were significantly reduced; IL-10 levels were increased and the CD4+/CD8+ T cell ratio was reduced. Conclusion Mare's milk can inhibit the inflammation of DSS-induced UC mice through immune regulation.

Expression of proBDNF/p75NTR in peripheral blood lymphocytes of patients with sepsis and its impact on lymphocyte differentiation / 中南大学学报(医学版)

Objective:Sepsis is a life-threatening organ dysfunction caused by the host's imbalanced response to infection.Due to lack of effective treatments,it has always been the difficulty and focus of clinical treatment of sepsis.Studies have shown that pro-brain-derived neurotrophic factor(proBDNF)binds to the high-affinity total neurotrophic factor p75 neurotrophin receptor(p75NTR),which activates downstream signaling cascades and disrupts immunological inflammation and plays an important role in the progression of sepsis.This study aims to explore the expression changes of lymphocyte-derived proBDNF/p75NTR in patients with sepsis and its effect on lymphocyte differentiation. Methods:From the healthy donors(control group,n=40)and sepsis patients(sepsis group,n=40)admitted to the hospital for the first time,peripheral blood samples and blood routine clinical detection indicators were obtained.By using flow cytometry,the proportion of lymphocyte subsets and their expression of proBDNF/p75NTR were examined.The peripheral blood lymphocytes were isolated from the control group and incubated with lipopolysaccharide(LPS).Flow cytometry analysis technology was used to detect the expression of proBDNF/p75NTR on LPS-treated lymphocyte subsets.On this basis,we investigated the effects on lymphocyte differentiation by inhibiting p75NTR. Results:White blood cell count,neutrophil count,and neutrophil percentage of the patients in the sepsis group at admission were significantly higher than those in the control group;on the contrary,lymphocyte count and lymphocyte percentage in the sepsis group were lower than those in the control group(all P＜0.001).The patients in the sepsis group had considerably greater neutrophil/lymphocyte and monocyte/lymphocyte ratios than those in the control group(both P＜0.05).In the peripheral blood of sepsis patients,proBDNF expression was upregulated on CD19+ B cells,whereas p75NTR expression was elevated on B cells,CD4+ T cells,and CD8+ T cells(all P＜0.05).ProBDNF/p75NTR expression was upregulated by LPS stimulation in vitro in peripheral blood cells of the control group(P＜0.05),and this tendency was similar to the expression alterations in peripheral lymphocytes of the sepsis group.Inhibition of p75NTR increased CD4+ T cell and CD19+ B cell percentages,cytokine expression of IL-4 and IL-10,and reduced IL-1β and IL-6 production(all P＜0.05). Conclusion:The immunosuppressive state of sepsis patients is indicated by a reduction in lymphocyte count and an increase in the proportion of inactive neutrophils.ProBDNF/p75NTR expression is upregulated in the peripheral blood lymphocytes of sepsis patients,and p75NTR inhibition may control lymphocyte differentiation involved in sepsis progression.

Protective effects of the salt-induced kinase inhibitor HG-9-91-01 on sepsis-associated cognitive dysfunction in mice and the underlying mechanisms / 中南大学学报(医学版)

Objective:Sepsis-associated cognitive dysfunction is a common complication in patients with sepsis and lack of effective treatment.Its pathological mechanisms remain unclear.Salt-induced kinase(SIK)is an important molecule in the regulation of metabolism,immunity,and inflammatory response.It is associated with the development of many neurological diseases.This study aims to investigate the expression of SIK in the hippocampus of septic mice,and to evaluate the role and mechanism of the SIK inhibitor HG-9-91-01 in sepsis-associated cognitive dysfunction. Methods:Firstly,C57BL/6 mice were randomly divided into a control group(Con group)and a sepsis model group[lipopolysaccharide(LPS)group].The model group was injected intraperitoneally with LPS at a dose of 8 mg/kg and the Con group was injected with an equal volume of normal saline.Hippocampal tissues were harvested at 1,3,and 6 days after injection and the expressions of SIK1,SIK2,and SIK3 were detected by real-time fluorescence quantitative PCR(qPCR)and Western blotting.Secondly,C57BL/6 mice were randomly divided into a Con group,a LPS group,and a SIK inhibitor group(HG group).The LPS and HG groups were injected with LPS to establish a sepsis model;in the HG group,HG-9-91-01(10 mg/kg)was injected intraperitoneally at 3-6 days after LPS injection,and the LPS group was injected with the same volume of vehicle.Cognitive function was assessed at 7-11 days after LPS injection using the Morris water maze(MWM).Hippocampal tissues were harvested after the behavioral tests,and the mRNA levels of inflammatory factors and microglial markers were assessed by qPCR.The protein levels of inducible nitric oxide synthase(iNOS),CD68,ionized calcium binding adaptor molecule 1(Iba-1),N-methyl-D-aspartate(NMDA)receptor(NR)subunit,cAMP response element-binding protein(CREB)-regulated transcription coactivator 1(CRTC1),and insulin-like growth factor 1(IGF-1)were detected by Western blotting.Immunohistochemistry(IHC)was used to detect the expression of Iba-1 positive cells in the CA1,CA3 and dentate gyrus(DG)of the hippocampus,followed by Sholl analysis. Results:Compared with the Con group,the mRNA and protein levels of SIK1,SIK2,and SIK3 in the hippocampus were increased in the LPS group(all P<0.05).Compared with the Con group,mice in the LPS group had a significantly longer escape latency,a lower percentage of target quadrant dwell time and a reduced locomotor speed(all P<0.05);the HG group had a decreased escape latency and an increased percentage of time spent in the target quadrant in comparison with the LPS group(both P<0.05).The mRNA levels of inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)],and the M1-type microglial markers iNOS and CD68 in the hippocampus of the LPS group were increased in comparison with the Con group,while the M2-type microglial markers CD206 and arginase-1(Arg-1)were decreased.Compared with the LPS group,the mRNA levels of TNF-α,IL-1β,IL-6,and iNOS were downregulated,while the levels of CD206 and Arg-1 were upregulated in the HG group(all P<0.05).The protein levels of iNOS,CD68,and Iba-1 in the hippocampus of the LPS group were increased in comparison with the Con group,but they were downregulated in the HG group in comparison with the LPS group(all P<0.05).The number of Iba-1 positive cells in CA1,CA3,and DG of the hippocampus was increased in the LPS group in comparison with the Con group,but they were decreased in the HG group in comparison with the LPS group(all P<0.05).Sholl analysis showed that the number of intersections at all radii between 8-38 μm from the microglial soma was decreased in the LPS group in comparison with the Con group(all P<0.05).Compared with the LPS group,the number of intersections at all radii between 14-20 μm was significantly increased in the HG group(all P<0.05).The protein levels of NR subunit NR1,NR2A,NR2B,and IGF-1 were downregulated in the hippocampus of the LPS group in comparison with the Con group,while the expression of phosphorylated CRTC1(p-CRTC1)was increased.Compared with the LPS group,the levels of NR1,NR2A,NR2B,and IGF-1 were upregulated,while p-CRTC1 was downregulated in the HG group(all P<0.05). Conclusion:SIK expression is upregulated in the hippocampus of septic mice.The SIK inhibitor HG-9-91-01 ameliorates sepsis-associated cognitive dysfunction in mice,and the mechanism may involve in the activation of the CRTC1/IGF-1 pathway,inhibition of neuroinflammation,and enhancement of synaptic plasticity.

Study on the Construction of Knowledge Graph Based on Breast Cancer Specialized Disease Database / 医学信息学杂志

Purpose/Significance To construct the ontology model of breast cancer knowledge graph,and to realize the structured expres-sion and visual display of breast cancer knowledge.Method/Processs Breast cancer knowledge is extracted and represented,and the ontology model of breast cancer knowledge graph is constructed by Protégé software.The model includes 5 types of entities including patient,basic infor-mation of patient,inspection,diagnosis and attribute value of inspection,and more than 10 kinds of relationships such as having,examining,diagnosing,belonging and so on.Result/Conclusion The graphical display of breast cancer knowledge helps to improve the public's attention and understanding of breast cancer,and has a positive effect on the prevention and health management of breast cancer.

Eplerenone protects contralateral kidney tissue from obstruction in pregnant rats with chronic kidney disease / 中国药理学通报

Aim To study the protective effect of eplerenone on the contralateral kidney in pregnant rats with chronic kidney disease (CKD) and its mechanism. Methods Female Wistar rats were randomly divided into sham-operation group, sham-operation pregnancy group, model group and eplerenone group. The rats in the model group and eplenone group had ligation unilateral ureter, and the rats in the eplenone group were treated with 100 mg • kg

Effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome based on 16S rDNA technique / 中国针灸

OBJECTIVES@#To explore the effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome (IBS-D) based on 16S rDNA technique.@*METHODS@#Ten rats were randomized from 58 SPF-grade male SD rats to be the blank group. The remained 48 rats were prepared to be IBS-D models by the modified method of acetic acid enema combined with binding tail-clip stress. Forty successfully-modeled rats were randomly divided into a model group, an acupuncture group, a moxibustion group and a western medication group, with 10 rats in each one. In the acupuncture group, the needle was inserted at bilateral "Zusanli" (ST 36) and remained for 15 min in each rat. In the moxibustion group, the suspending moxibustion was delivered at bilateral "Zusanli" (ST 36) for 15 min. The rats in the western medication group were given pinaverium bromide suspension (10 mL/kg) by intragastric administration. The above interventions were performed once daily for consecutive 14 days. The body mass and the score of fecal trait were compared before and after modeling, as well as after intervention in each group. Fecal water content, diarrhea index and colon transit time (CTT) were measured after modeling and intervention in the rats of each group separately. After intervention, the colonic morphology of rats in each group was observed, and using 16S rDNA technique, the intestinal flora was detected.@*RESULTS@#After modeling, compared with the blank group, the body mass and CTT were reduced (P<0.01); fecal trait scores, fecal water contents and diarrhea index increased (P<0.01) in the other 4 groups. After intervention, the body mass and CTT of the rats decreased (P<0.01), and fecal trait score, fecal water content and diarrhea index increased (P<0.01) in the model group compared with those in the blank group. In the acupuncture group, the moxibustion group and the western medication group, when compared with the model group, the body mass and CTT were elevated (P<0.01), while fecal trait scores, fecal water contents and diarrhea index declined (P<0.01). Compared with the western medication group, fecal water content decreased in the acupuncture group and the moxibustion group (P<0.05), while CTT increased in the acupuncture group (P<0.01), the body mass increased and fecal trait score was dropped in the moxibustion group (P<0.05). The colonic mucosa structure was clear and complete, and there was no obvious inflammatory cell infiltration in the blank group. The mild interstitial edema of intestinal mucosa was presented with the infiltration of few inflammatory cells in the model group. There was the infiltration of few inflammatory cells in the mucosa of the acupuncture group, the moxibustion group and the western medication group. Compared with the blank group, the indexes of Richness, Chao1, ACE and Shannon decreased in the model group (P<0.05). Indexes of Richness, Chao1 and ACE increased in the acupuncture group and the moxibustion group (P<0.05), and the Richness index in the western medication group increased (P<0.05) when compared with those in the model group. The relative abundance of Bacteroidetes, Proteobacteria and Prevotella increased (P<0.05), and that of Firmicutes and Muribaculaceae decreased (P<0.05) in the model group compared with those in the blank group. When compared with the model group, the relative abundance of Bacteroidetes, Proteobacteria and Prevotella was reduced (P<0.05), while that of Firmicutes and Muribaculaceae increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group; and that of Actinobacteria and Bifidobacterium increased in the acupuncture group and the moxibustion group (P<0.05). Compared with the blank group, the relative abundance of lipopolysaccharide (LPS) biosynthesis was elevated (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis decreased (P<0.05) in the model group. The relative abundance of LPS biosynthesis was dropped (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group compared with those of the model group.@*CONCLUSIONS@#Either acupuncture or moxibustion can relieve the symptoms of IBS-D and protect intestinal mucosa, which may be associated with regulating the structure of intestinal flora and promoting nutrient metabolism and biosynthesis.

Observation of the Curative Effect of the Dexamethasone Vitreous Cavity Implant for the Treatment of Irvine-Gass Syndrome / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the clinical efficacy of dexamethasone vitreous cavity implants (Ozurdex) for the treatment of macular edema (Irvine-Gass Syndrome) after cataract surgery.@*METHOD@#Eight patients (eight eyes) with Irvine-Gass syndrome were enrolled for vitreous injections with Ozurdex. The patients included six men (six eyes) and two women (two eyes) with a mean age of 67.12 ± 11.92 years. Changes in the patients best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure were compared before and after treatment.@*RESULT@#The mean visual acuity BCVA of the patients was 0.81 ± 0.26 before implantation, which improved to 0.20 ± 0.12, 0.13 ± 0.09, and 0.15 ± 0.13 at 2 weeks, 1 month, and 3 months after implantation, respectively ( P < 0.001). The patient's mean CMT before implantation was 703.00 ± 148.88 μm, and it reduced to 258.87 ± 37.40 μm, 236.25 ± 28.74 μm, and 278.00 ± 76.82 μm at 2 weeks, 1 month, and 3 months after implantation, respectively ( P < 0.001).@*CONCLUSION@#The dexamethasone vitreous cavity implant (Ozurdex) is a safe and effective treatment, which can effectively improve patient's visual acuity and reduce macular edema associated with cataract surgery.

A Campylobacteriosis Outbreak Caused by One Asymptomatic Food Handler Carrier / 生物医学与环境科学（英文）

In August 2021, three students with diarrhea from the same school visited a local hospital in the S district of Beijing. An epidemic investigation showed that there were more students with diarrhea in the same school and they had one meal together. Campylobacter jejuni was isolated from both patients with diarrhea and asymptomatic food handlers; however, the latter also carried Campylobacter coli. Phylogenomic analysis showed that there was a campylobacteriosis outbreak among the students, and the asymptomatic food handler may have been the source of the infection. Routine inspection and surveillance for Campylobacter is needed for the food producing staff, particularly those cooking in the cafeteria in schools or other public food services.

Quality analysis of Codonopsis pilosula with different commodity specification grades / 中国药房

OBJECTIVE To study the quality of Codonopsis pilosula with different commodity specification grades， and to provide the data support for market transactions， scientific research and clinical use. METHODS According to the classification standard of commodity specification grades of C. pilosula， 17 batches of C. pilosula from different producing areas， origins and commodity specification grades were collected. The contents of tangshenoside Ⅰ， lobetyolin and atractylenolide Ⅲ were determined by HPLC. The contents of alcohol-soluble extracts were determined by hot dipping method stated in general rule 2201 of Chinese Pharmacopeia （part Ⅳ）. The contents of polysaccharide were determined by phenol-sulfuric acid method （calculated by D-glucose anhydrous）. RESULTS For cultivar of C. pilosula， four specifications and three commodity grades of C. pilosula all contained tangshenoside Ⅰ and lobetyolin； Radix C. pilosula from Shanxi of China and C. pilosula from Wenxian County of China， also contained atractylenolide Ⅲ. In terms of the contents of tangshenoside Ⅰ， lobetyolin and atractylenolide Ⅲ， the content of second class was equivalent to that of first class， even better than the first class， while the content of third class was lower than that of first class and second class； the content of tangshenoside Ⅰ was the highest among the two types of wild C. pilosula. The contents of alcohol-soluble extracts and polysaccharides in first class cultivated C. pilosula were higher than those of second class， and the second class was higher than the third class； wild C. pilosula had low content of alcohol-soluble extracts and polysaccharides. CONCLUSIONS The internal quality of C. pilosula is basically consistent with the classification standard of different commodity specification grades； the content of each indicator in first-class and second-class medicinal herb is high， making them high-quality medicinal herbs.