miR-9500 Regulates Migration and Invasion of Lung Adenocarcinoma Cells by Targeting SMAD2 / 肿瘤防治研究

Objective To explore the molecular mechanism underlying miR-9500 regulating the migration and invasion of lung adenocarcinoma cells by targeting SMAD2. Methods The core target genes of miR-9500 were screened out by bioinformatics analysis, and their GO function analysis, KEGG signaling pathway enrichment, and survival analysis were performed. The targeted binding sites between miR-9500 and SMAD2 were predicted, and the direct targeting relationship between miR-9500 and SMAD2 was verified by dual-luciferase reporter assay. qRT-PCR and Western blot were used to assess the effect of miR-9500 on the mRNA and protein expression levels of SMAD2. Wound healing assay, Transwell assay, and Matrigel invasion assay were used to determine the effect of miR-9500 on the migration and invasion of lung adenocarcinoma cells. Results The core target genes of miR-9500 were mainly enriched in the cancer pathway, TGF-β signaling pathway, and focal adhesion. However, only the expression levels of VAMP2, SMAD2, and RXRA among the top 10 core target genes were significantly correlated with the overall survival of patients with lung adenocarcinoma. miR-9500 targeted SMAD2 and down-regulated the expression levels of SMAD2, and overexpression of miR-9500 significantly inhibited the migration and invasion of lung adenocarcinoma cells and markedly decreased the expression levels of MMP2 and MMP9. Conclusion miR-9500 can inhibit the migration and invasion of lung adenocarcinoma cells by targeting SMAD2, which may play an important role in the tumorigenesis and development of lung adenocarcinoma as a tumor suppressor.

Prognosis analysis of radical or modified radical hysterectomy and simple hysterectomy in patients with stage Ⅱ endometrial cancer / 中华妇产科杂志

Objective: To compare the prognosis and perioperative situation of patients with stage Ⅱ endometrial cancer (EC) between radical hysterectomy/modified radical hysterectomy (RH/mRH) and simple hysterectomy (SH). Methods: A total of 47 patients diagnosed EC with stage Ⅱ [International Federation of Gynecology and Obstetrics (FIGO) 2009] by postoperative pathology, from January 2006 to January 2021 in Peking University People's Hospital, were analyzed retrospectively. The patients were (54.4±10.7) years old, and the median follow-up time was 65 months (ranged 9-138 months). They were divided into RH/mRH group (n=14) and SH group (n=33) according to the scope of operation. Then the prognosis of patients between the groups were compared, and the independent prognostic factors of stage Ⅱ EC were explored. Results: (1) The proportions of patients with hypertension in RH/mRH group and SH group were 2/14 and 45% (15/33), the amounts of intraoperative blood loss were (702±392) and (438±298) ml, and the incidence of postoperative complications were 7/14 and 15% (5/33), respectively. There were significant differences (all P<0.05). (2) The median follow-up time of RH/mRH group and SH group were 72 vs 62 months, respectively (P=0.515). According to Kaplan-Meier analysis and log-rank method, the results showed that there were no significant difference in 5-year progression-free survival (PFS) rate (94.3% vs 84.0%; P=0.501), and 5-year overall survival rate (92.3% vs 92.9%; P=0.957) between the two groups. Cox survival analysis indicated that age, pathological type, serum cancer antigen 125 (CA125), and estrogen receptor (ER) status were associated with 5-year PFS rate (all P<0.05). But the scope of hysterectomy (RH/mRH and SH) did not affect the 5-year PFS rate of stage Ⅱ EC patients (P=0.508). And level of serum CA125 and ER status were independent prognostic factors for 5-year PFS rate (all P<0.05). Conclusions: This study could not find any survival benefit from RH/mRH for stage Ⅱ EC, but increases the incidence of postoperative complications. Therefore, the necessity of extending the scope of hysterectomy is questionable.

Molecular mechanism of resveratrol combined with irinotecan in treatment of colorectal cancer / 中国中药杂志

This study aimed to investigate the mechanism of resveratrol(RES) combined with irinotecan(IRI) in the treatment of colorectal cancer(CRC). The targets of RES, IRI, and CRC were obtained from databases, and the targets of RES combined with IRI in the treatment of CRC were acquired by Venn diagram. The protein functional cluster analysis, GO and KEGG enrichment analyses were performed. In addition, the protein-protein interaction(PPI) network was constructed. The core target genes were screened out and the target-signaling pathway network was set up. IGEMDOCK was used to dock the core target gene molecules. Besides, the relationship between the expression level of key target genes and the prognosis and immune infiltration of CRC was analyzed. Based on the in vitro cell experiment, the molecular mechanism of RES combined with IRI in the treatment of CRC was explored and analyzed. According to the results, 63 potential targets of RES combined with IRI were obtained for CRC treatment. Furthermore, cluster analysis revealed that protein functions included 23% transmembrane signal receptors, 22% protein modifying enzymes, and 14% metabolite converting enzymes. GO analysis indicated that BPs were mainly concentrated in protein autophosphorylation, CCs in receptor complex and plasma membrane, and MFs in transmembrane receptor protein tyrosine kinase activity. Moreover, KEGG signaling pathways were mainly enriched in central carbon metabolism in cancer. The key targets of RES combined with IRI in the treatment of CRC were PIK3CA, EGFR, and IGF1R, all of which were significantly positively correlated with the immune infiltration of CRC. As shown by the molecular docking results, PIK3CA had the most stable binding with RES and IRI. Compared with the results in the control group, the proliferation ability and EGFR protein expression of CRC cells in the RES-treated group, the IRI-treated group, and the RES+IRI treated group significantly decreased. Moreover, the cell proliferation ability and EGFR protein expression level of CRC cells in the RES+IRI treated group were remarkably lower than those in the IRI-treated group. In conclusion, PIK3CA, EGFR, and IGF1R are the key targets of RES combined with IRI in CRC treatment. In addition, RES can inhibit the proliferation of CRC cells and improve IRI chemoresistance by downregulating the EGFR signaling pathway.

Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace / 中西医结合学报

OBJECTIVE@#This study investigated trends in the study of phytochemical treatment of post-traumatic stress disorder (PTSD).@*METHODS@#The Web of Science database (2007-2022) was searched using the search terms "phytochemicals" and "PTSD," and relevant literature was compiled. Network clustering co-occurrence analysis and qualitative narrative review were conducted.@*RESULTS@#Three hundred and one articles were included in the analysis of published research, which has surged since 2015 with nearly half of all relevant articles coming from North America. The category is dominated by neuroscience and neurology, with two journals, Addictive Behaviors and Drug and Alcohol Dependence, publishing the greatest number of papers on these topics. Most studies focused on psychedelic intervention for PTSD. Three timelines show an "ebb and flow" phenomenon between "substance use/marijuana abuse" and "psychedelic medicine/medicinal cannabis." Other phytochemicals account for a small proportion of the research and focus on topics like neurosteroid turnover, serotonin levels, and brain-derived neurotrophic factor expression.@*CONCLUSION@#Research on phytochemicals and PTSD is unevenly distributed across countries/regions, disciplines, and journals. Since 2015, the research paradigm shifted to constitute the mainstream of psychedelic research thus far, leading to the exploration of botanical active ingredients and molecular mechanisms. Other studies focus on anti-oxidative stress and anti-inflammation. Please cite this article as: Gao B, Qu YC, Cai MY, Zhang YY, Lu HT, Li HX, Tang YX, Shen H. Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace. J Integr Med. 2023; 21(4):385-396.

Hydroxysafflor yellow A inhibits proliferation, migration, and chemoresistance of colorectal cancer cells through Akt/mTOR-autophagy pathway / 中国中药杂志

In recent years, the clinical treatment of colorectal cancer(CRC) has made great progress, but chemoresistance is still one of the main reasons for reducing the survival rate of patients with colorectal cancer. Therefore, ameliorating chemotherapy resis-tance is an urgent problem to be solved. The purpose of this study was to investigate the regulatory role and related molecular mechanisms of hydroxysafflor yellow A(HSYA) in colorectal cancer cell proliferation, migration, and 5-fluorouracil(5-FU) chemoresistance. In this study, HCT116 and HT-29 cells were used as research subjects. Firstly, methyl thiazolyl tetrazolium(MTT) assay and colony formation assay were used to detect and analyze the effect of HSYA on the proliferation of CRC cells. Secondly, the effect of HSYA on the cell cycle in CRC cells was analyzed by cell cycle assay. Furthermore, the effect of HSYA on the migration of CRC cells was analyzed by wound-healing assay and Transwell assay. Based on the above, the influences of HSYA on 5-FU chemoresistance of CRC cells and related molecular mechanisms were explored and analyzed. The results showed that HSYA significantly inhibited the proliferation and migration of CRC cells, and arrested the cell cycle in G_0/G_1 phase. In addition, HSYA significantly ameliorated the chemoresistance of CRC cells to 5-FU. The results of acridine orange staining and Western blot showed that the autophagy activity of CRC cells in the HSYA and 5-FU combined treatment group was significantly higher than that in the 5-FU single drug treatment group. As compared with the 5-FU single drug treatment group, the phosphorylation levels of protein kinase B(Akt) and mammalian target of rapamycin(mTOR) in the HSYA and 5-FU combined treatment group were significantly reduced, indicating that the Akt/mTOR signaling pathway in the combined treatment group was down-regulated in CRC cells. In conclusion, HSYA may upregulate autophagy activity through the Akt/mTOR signaling pathway, thereby inhibiting the proliferation and migration of CRC cells and ameliorating the chemoresistance to 5-FU.

Dissection of Cellular Communication between Human Primary Osteoblasts and Bone Marrow Mesenchymal Stem Cells in Osteoarthritis at Single-Cell Resolution

Background and Objectives@#Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and playimportant role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs in vivo in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells. @*Methods@#and Results: To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identifynew cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found FZD1 was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and SFRP4, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs. @*Conclusions@#Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.

Gallic Acid Ameliorates Cognitive Impairment Caused by Sleep Deprivation through Antioxidant Effect

Sleep deprivation (SD) has a profound impact on the central nervous system, resulting in an array of mood disorders, including depression and anxiety. Despite this, the dynamic alterations in neuronal activity during sleep deprivation have not been extensively investigated. While some researchers propose that sleep deprivation diminishes neuronal activity, thereby leading to depression. Others argue that short-term sleep deprivation enhances neuronal activity and dendritic spine density, potentially yielding antidepressant effects. In this study, a two-photon microscope was utilized to examine the calcium transients of anterior cingulate cortex (ACC) neurons in awake SD mice in vivo at 24-hour intervals. It was observed that SD reduced the frequency and amplitude of Ca2+ transients while increasing the proportions of inactive neurons. Following the cessation of sleep deprivation, neuronal calcium transients demonstrated a gradual recovery. Moreover, whole-cell patch-clamp recordings revealed a significant decrease in the frequency of spontaneous excitatory post-synaptic current (sEPSC) after SD. The investigation also assessed several oxidative stress parameters, finding that sleep deprivation substantially elevated the level of malondialdehyde (MDA), while simultaneously decreasing the expression of Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) and activities of Superoxide dismutase (SOD) in the ACC. Importantly, the administration of gallic acid (GA) notably mitigated the decline of calcium transients in ACC neurons. GA was also shown to alleviate oxidative stress in the brain and improve cognitive impairment caused by sleep deprivation. These findings indicate that the calcium transients of ACC neurons experience a continuous decline during sleep deprivation, a process that is reversible. GA may serve as a potential candidate agent for the prevention and treatment of cognitive impairment induced by sleep deprivation.

Effects of heat stress on intestinal tract and cognitive function / 环境与职业医学

Heat stress refers to a series of stress reactions such as heat balance disturbance and physiological dysfunction when the body is exposed to the thermal environment for a long time. Studies have found that heat stress can damage intestinal morphology, such as length of intestinal villi, number of goblet cells, and depth of the crypt, affecting the digestion and absorption functions. It also can increase the permeability of the intestinal barrier by damaging the tight junction of the intestinal epithelium, which in turn allows endotoxin and bacteria to enter the blood circulation from the intestinal cavity to cause a systemic inflammatory response. At the same time, heat stress can disrupt the homeostasis of intestinal microbiota, increase pathogenic bacteria, and change downstream metabolites such as short-chain fatty acids. In addition, heat stress can inhibit the occurrence of hippocampal neurons and reduce the number of neurons; decrease the density of synapses; damage important organelles of neurons; induce inflammation of the central nervous system, and then lead to cognitive dysfunction. The brain-gut axis is a two-way signal axis between the intestine and the brain. Intestinal microorganisms and the intestinal barrier can participate in central nervous system regulation, and the brain can change the intestinal homeostatic function and affect the quality of the intestinal barrier through the hypothalamic-pituitary-adrenal axis (HPA axis). The interaction plays an essential role in the body's homeostasis. Therefore, this article reviewed current understandings on the impacts of heat stress on the gut and cognitive function, aiming to provide a reference for subsequent research.

Factors affecting medical device management in COVID-19 pandemic / 中华医院管理杂志

Objective:To explore the factors affecting the management of medical devices in the COVID-19 pandemic, and to provide guidance for the management of medical devices in public health emergencies.Methods:A total of 184 hospitals caring COVID-19 patients in Jiangsu, Zhejiang, Shanghai, Anhui and Shandong were selected, and clinical engineers were randomly sampled. A self-compiled questionnaire was used to conduct an online survey on factors affecting medical device management during the COVID-19 pandemic from August to December 2021.The index system of influencing factors of medical device management during the COVID-19 pandemic was determined through an exploratory factor analysis, and then the structural equation model was used to verify the rationality and scientificity of the index system, while the relative weight method was used to calculate the weight of the index system.Results:277 valid questionnaires were recovered. Through the exploratory factor analysis, an index system of influencing factors of medical device management was established, which consisted of such level-indexes as the human factor, device factor, material factor, method factor, and environment factor, as well as 17 level-2 indexes. The fitness-indexes of the second-order structural equation model were finally fitted as follows: the chi-square to freedom ratio was 2.606, the approximate root mean square error was 0.076, and the value of value-added adaptation index, non-standard adaptation index and comparative adaptation index were 0.921, 0.903 and 0.920, respectively. The weights of the method factor, human factor, device factor, material factor and environment factor of the level-1 indexes were 0.216, 0.191, 0.175, 0.274 and 0.144, respectively. Such factors as manpower, regulations and institutional processes, and information technology ranked top three among the 17 level-2 indexes, which were 0.090, 0.082 and 0.080 respectively.Conclusions:The influencing factor model of medical device management during the COVID-19 pandemic in this study is ideal; human factors and method factors are the influencing factors deserving high priority in medical device management during the COVID-19 pandemic. Ensuring sufficient human resources, improving laws, regulations and processes, as well as enhancing information management level are breakthroughs expected in medical device management.

Application of ultrasound monitoring optic nerve sheath diameter in diagnosis and treatment of adult patients with intracranial hypertension / 中国医师进修杂志

Objective:To investigate the effect of ultrasound measurement of optic nerve sheath diameter (ONSD) in adult patients with elevated intracranial pressure (ICP).Method:From June 2017 to March 2020, A total of 64 patients (32 patients with elevated ICP and 32 patients with normal ICP) were placed with invasive intracranial pressure monitoring probe in Beijing Pinggu Hospital. Their ICP and ONSD were continuously monitored. Thirty-two healthy volunteers were recruited as control group to check ONSD. The correlation between ONSD and ICP, and the changes of ICP and ONSD after osmotic therapy were observed.Results:The ONSD in ICP increased group was significantly higher than that in normal ICP group: (5.77 ± 0.3) mm vs. (5.01 ± 0.1) mm, with statistical difference ( P<0.05), and there was a positive correlation between ONSD and ICP. There was no significant difference in ONSD between normal ICP group and control group ( P>0.05). Conclusions:Ultrasound monitoring ONSD can reflect the level of ICP and evaluate the effect of osmotic therapy and the prognosis of patients. Bedside ultrasound examination of optic nerve sheath diameter could be used to judge ICP and to evaluate the curative effect of osmotic therapy, with high clinical application value.

Waist circumference predicts the risk of hypertension in overweight and non-overweight middle school students in Suzhou / 公共卫生与预防医学

Objective To explore the ability of waist circumference (WC) to predict hypertension risk in overweight and non-overweight middle school students in Suzhou. Methods The height, weight，WC and blood pressure values of 963 students from 8 middle schools in Suzhou were collected by a combination of questionnaire survey and physical examination. Logistic regression analysis was applied to explore the correlation between WC and high blood pressure in middle school students. Results Logistic regression analysis showed that before and after adjusting for confounding factors, for every 1 cm change in WC, the risk of high blood pressure increased to 1.08 (1.03-1.14) and 1.07 (1.02-1.13) for non-overweight students, and 1.05 (1.02-1.09) and 1.05 (1.01-1.08) for overweight students, respectively. Conclusion There was a positive correlation between WC and high blood pressure in both non-overweight and overweight middle school students in Suzhou. The risk of high blood pressure was higher for non-overweight students than overweight students for every 1 cm WC change. Targeted intervention measures should be taken to reduce the prevalence rates of hypertension for middle school students.

Prevalence of hypertension based on three separate visits among primaryand middle school students in Suzhou City / 预防医学

Objective@#To investigate the prevalence of hypertension among primary and middle school students living in Suzhou City, Jiangsu Province, so as to provide insights into comprehensive hypertension control among children and adolescents.@*Methods@# Primary and middle school students at ages of 7 to 17 years were recruited for a questionnaire survey in Suzhou City using the stratified cluster random sampling method from September to December, 2020, and the height and body weight were measured. Blood pressure was measured at three separate clinic visits according to the national criteria Reference of Screening for Elevated Blood Pressure among Children and Adolescents Aged 7-18 Years ( WS/T 610-2018 ), and the detection of elevated blood pressure was estimated at three separate visits. In addition, factors affecting elevated blood pressure were identified. @*Results@#A total of 3 713 students were enrolled, including 1 924 boys ( 51.82% ) and 1 789 girls ( 48.18% ). The detection of elevated blood pressure was 13.63%, 5.36%, and 3.37% at three separate visits, respectively, and the prevalence of hypertension ( elevated blood pressure at all three visits ) was 3.37%. The detection rates of elevated blood pressure were all higher at three visits ( 16.90%, 8.40%, and 5.26% ) among students at ages of 12 to 17 years than among students at ages of 7 to 11 years ( 9.65%, 1.67%, and 1.07%, P<0.05 ). The detection of elevated blood pressure was significantly higher in boys ( 15.23% ) than in girls (11.91%) at the first visit ( P<0.05 ), while no significant differences were seen at the second or third visit ( P>0.05 ). In addition, higher detection rates of elevated blood pressure were seen in obese ( 27.62%, 11.51%, and 7.06% ) and overweight students ( 17.45%, 6.95%, and 4.85% ) than in students with normal weight ( 9.44%, 3.54%, and 2.15% ) at all three visits, and greater detection rates of elevated blood pressure were found in obese students than in overweight students at the first and second visits ( P<0.017 ).@*Conclusions @#The prevalence of hypertension was 3.37% based on three separate visits among primary and middle school students in Suzhou City. Measurement of blood pressure at three separate visits within different days is effective to reduce the false positive rate of hypertension and decrease misdiagnosis among children and adolescents.

A plateform for management of atrial fibrillation based on internet and medical concortium / 中华全科医师杂志

In order to provide efficient medical care to atrial fibrillation patients in the community, the Huamu Community Health Service Center in association with its medical consortium, Renji Hospital have developed a novel atrial fibrillation management system. With the collaboration of general practitioners and specialist team from the tertiary hospital, a special clinic for atrial fibrillation has been set up in the community health service center, which is based on the internet technology and the medical consortium platform. This article introduces the development of this novel system and the initial outcome of the measures, to provide a reference for the management of atrial fibrillation patients in the community.

Regulation and mechanism of Myosin X on radiosensitivity of non-small cell lung cancer cell line H1975 in vitro / 中华放射肿瘤学杂志

Objective:To investigate the effect and mechanism of Myosin X on the radiosensitivity of non-small cell lung cancer (NSCLC) cell line H1975 in vitro. Methods:Western blot was applied to detect the expression level of Myosin X expression. The H1975 cell line with stable knockout of Myosin X (KO group) and infected with control virus (NC group) were constucted by using CRISPR/Cas9 technique. The knockout efficiency was validated. The radiosensitivity of two cell lines was measured by colony formation assay and single-hit multi-target model. γ-H 2AX focus formation test and RNA sequencing (RNAseq) analysis were employed to identify the regulatory mechanism of the radiosensitivity of lung cancer cell lines mediated by Myosin X. Results:The expression level of Myosin X in the H1975 cells was significantly up-regulated than those in other NSCLC cell lines (all P<0.01). The lentiviral vector of Myosin X sgRNA-Lenti-CRISPR v2 was successfully constructed. After the puromycin screening, H1975 cell lines with complete knockout of Myosin X and control cell lines (NC group) were obtained. Colony formation assay demonstrated that compared with the NC group, the radiosensitivity in the KO group was significantly higher (The D 0 value was decreased from 1.28 Gy to 1.03 Gy, SF 2 decreased from 0.29 to 0.21, and the sensitization ratio was 1.24). The γ-H 2AX focus formation test showed that the number of damage focus formed at 1 h and 6 h after irradiation in the KO group was significantly larger than that in the NC group ( P<0.05. RNAseq analysis indicated that the expression level of ISLR in the KO group was significantly down-regulated than that IN the NC group ( P<0.05). Conclusion:Knockout of Myosin X can increase the radiosensitivity of H1975 cells probably by interfering the repair of DNA double-strand damage and down-regulating the expression level of ISLR.

Effect of CDK1 Interferes with the Regulation of PLK1, Aurora B and TRF1 on the Proliferation of Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of CDK1 interference regulation of PLK1, Aurora B and TRF1 on the proliferation of leukemia cells.@*METHODS@#The human myelogenous leukemia cell line HL-60 was selected as the research object, and the effect of TRF1 expression and its changes on cell proliferation and cycle was investigated by regulating intracellular CDK1 expression. The objects were divided into 5 groups, including control group, shRNA-NC group, CDK1-shRNA group, pcDNA group and pcDNA-CDK1 group. RT-PCR was used to detect the CDK1 expression of cells in each group; colony formation was used to detect the proliferation of the cells. Western blot was used to detect the expression of CDK1, PLK1, Aurora B, TRF1, and cyclin p53, p27, cyclinA.@*RESULTS@#The phosphorylation level of PLK1, Aurora B and the expression of TRF1 in the CDK1-shRNA group were significantly down-regulated as compared with those in the control group (P<0.05). Compared with the control group, the cells in CDK1-shRNA group showed lower clone formation rate, the increasing of cycle-associated proteins p53 and p27 and the decreasing of cyclinA expression (P<0.05). It was shown that interfered CDK1 expression could inhibit the proliferation of HL-60 cells and prolong the time that they enter mitosis, thereby extending the cell cycle. Compared with the control group, the overexpressed CDK1 in the pcDNA-CDK1 group made the phosphorylation level of PLK1, Aurora B, and TRF1 expression increase significantly (P<0.05), also the colony formation rate (P<0.05). The cycle-related proteins p53 and p27 was down-regulated, while cyclinA expression was up-regulate significantly (P<0.05). The results indicted that overexpressed CDK1 could stimulate adverse reactions, thereby promoting the proliferation of HL-60 cells and shortening the cell cycle.@*CONCLUSION@#Knocking out CDK1 can inhibit the phosphorylation of PLK1 and Aurora B and negatively regulate TRF1, thereby inhibiting the proliferation of leukemia cells.

Hotspot Analysis of Traditional Drugs in Diabetes Treatment Literature / 中国结合医学杂志

OBJECTIVE@#To summarize current hotspots and predict the potential trends in traditional drugs of diabetes treatment for further research.@*METHODS@#Publications on the application of traditional drugs in diabetes treatment were searched from PubMed without language limits. Highly frequent MeSH terms were identified through Bibliographic Item Co-Occurrence Matrix Builder (BICOMB). Biclustering analysis results were visualized utilizing the gCLUTO software. Finally, a strategic diagram was generated.@*RESULTS@#Totally 2,386 relevant publications were obtained from PubMed on November 9th, 2018, and 69 highly frequent MeSH terms were identified. Biclustering analysis revealed that these highly frequent MeSH terms were classified into 7 clusters. After calculating the density and centrality of each cluster, strategy diagram was presented. Cluster 0 "Chinese medicine monomers such as antioxidant and hypoglycemic effects" was considered as the most potential research hotspot.@*CONCLUSIONS@#In this study, we found 7 topics related to the application of traditional drugs in diabetes treatment. The molecular mechanisms of Chinese medicine monomers in diabetes could become a potential hotspot with high centricity and low density.

Studies on resistance of Schistosoma to praziquantel XVIII Sensitivity to praziquantel in filial generations of praziquantel-resistant and -sensitive Schistosoma japonicum mixed infections / 中国血吸虫病防治杂志

Objective To investigate the sensitivity of adult worms of filial generations from praziquantel-resistant and -sensitive Schistosoma japonicum mixed infections to praziquantel. Methods Mice were infected with the cercariae of an experimentally generated praziquantel-resistant S. japonicum isolate [median effective dose (ED50) = 277.4 mg/kg] and a laboratory-maintained praziquantel-sensitive S. japonicum isolate (ED50 = 99.6 mg/kg) at a mixture ratio of 1:1 and 2:1, which was maintained in the laboratory via the mouse-snail cycle for 8 generations. Then, mice were infected with the cercariae of the 8th filial-generation parasite, and grouped 35 days post-infection. Mice in the 5 treatment groups were given praziquantel treatment by gavage at a single oral dose of 37.5, 75, 150, 300 mg/kg and 600 mg/kg, while animals in the control group was administered orally with 2.5% cremophor EL. All mice were sacrificed 14 days post-treatment and adult worms were collected by perfusion of the portal vein. The worm burden reductions and praziquantel ED50 values were calculated. The praziquantel-resistant S. japonicum isolate generated from experimental induction with 12 rounds of praziquantel treatment with sub-curative doses was maintained in the laboratory via the mouse-snail cycle, and mice were infected with the cercariae of the 8th filial-generation parasite. The praziquantel ED50 value against the 8th filial-generation adults was measured. Results After mice were infected with the mixture of cercariae of PZQ-resistant and -sensitive S. japonicum isolates at a ratio of 1:1, the praziquantel ED50 was 135.2 mg/kg against the adults of the 8th filial-generation parasite. After mice were infected with the mixture of cercariae of PZQ-resistant and -sensitive S. japonicum isolates at a ratio of 2:1, the praziquantel ED50 was 129.2 mg/kg against the adults of the 8th filial-generation parasite. In addition, the praziquantel ED50 was 208.4 mg/kg against the adults of the 8th filial-generation S. japonicum without the selection pressure of praziquantel. Conclusions Compared with the experimentally induced praziquantel-resistant S. japonicum isolate, the adult worms of the filial-generation S. japonicum show a reduced sensitivity to praziquantel in the same host following infection with the mixture of cercariae of praziquantel-resistant and -sensitive S. japonicum isolates. The adult worms of the filial generation of the praziquantel-resistant S. japonicum isolate without the selection pressure of praziquantel may still maintain the resistance to praziquantel.

Investigation on Schistosoma japonicum infection in goats in Dantu District, Zhenjiang City from 2004 to 2019 / 中国血吸虫病防治杂志

Objective To investigate the prevalence and changing patterns of Schistosoma japonicum infections in goats in Dantu District of Zhenjiang City, so as to provide the scientific data for the management of in livestock. Methods The S. japonicum infections were detected using a miracidial hatching test (one test for one stool specimen) in goats grazed in settings with snail habitats in Dantu District of Zhenjiang City at spring and autumn of each year from 2004 to 2019, and the prevalence and intensity of S. japonicum infections were estimated. Results A total of 21 836 goat stool samples were detected from 2004 to 2019, and 86 were positive for S. japonicum (0.39% prevalence). The highest prevalence of S. japonicum infections in goats was seen in 2004 (1.25%) and no infections were detected in goats since 2013. S. japonicum-infected goats were identified in marshland-type endemic areas and plain regions with waterway networks, and there was a significant difference in the prevalence of S. japonicum infections in goats between these two types of endemic areas (0.50% vs. 0.15%; χ2 = 11.566, P < 0.05). The prevalence of S. japonicum infections was significantly greater in goats at ages of more than 10 months (0.51%) and over 10 months (0.44%) than in other goats (χ2 = 13.088, P < 0.05), and higher prevalence was found in autumn than in spring (0.54% vs. 0.27%; χ2 = 9.597, P < 0.05). In addition, there were 76.74% of S. japonicum-infected goats with intensity of“+++”and“++++”. Conclusions Although the high prevalence of S. japonicum infections has been effectively controlled in goats in Dantu District, goat remains to be an important source of S. japonicum infections that should be given a high priority for control to consolidate the schistosomiasis control achievements.

Anti-inflammatory study on 9,9'-O-di-(E）-feruloyl-meso-5,5'-dimethoxysecoisolariciresinol (LCA), an active ingredient in Litsea cubeba (Lour.) Pers / 药学实践杂志

Objective To evaluate the anti-inflammatory effects of LCA, which is the active component from Litsea cubeba (Lour.) Pers. Methods Pharmacodynamic evaluations of ear swelling and cotton ball granuloma models were used in animal experiments. In vitro experiment, lipopolysaccharide (LPS) stimulated monocyte macrophage RAW264.7 cells were used to evaluate the anti-inflammatory activity of LCA by detecting the secretions of nitric oxide (NO), tumor necrosis factor-α (TNF-α), the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein. Results In ear swelling experiment, the extent of ear swelling was significantly lower in the LCA treated group than the model group. The inhibition rate was greater in the high LCA concentration group than the positive drug group. In addition, LCA reduced the weight of cotton ball granuloma markedly. At the cell level, LCA significantly inhibited the secretions of NO, TNF-α and reduced the expressions of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells. Conclusion LCA has significant anti-inflammatory effects in vitro and in vivo. The further studies are warranted for the development of anti-inflammatory drugs.

Role of hippocampal HO-1 in electroacupuncture-induced reduction of lipopolysaccharide-induced brain injury in mice / 中华麻醉学杂志

Objective:To evaluate the role of hippocampal hemeoxygenase-1 (HO-1) in electroacupuncture (EA)-induced reduction of lipopolysaccharide (LPS)-induced brain injury in mice.Methods:Twenty-four healthy adult C57BL/6J mice of both sexes, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), LPS-induced brain injury group (LPS group), LPS plus EA group, and LPS plus EA plus HO-1 inhibitor zinc protoporphyria (ZnPP) group (LPS+ EA+ ZnPP group). A virus carrying calcium ion fluorescent probes was injected into and an optical fiber was implanted into the hippocampal CA1 region to record changes in the calcium fluorescence signals.Three weeks later, Baihui, Quchi and Zusanli acupoints were stimulated with constant voltage (2/15 Hz) and disperse-dense waves for 30 min once a day for 5 consecutive days, and the stimulation intensity was defined as less than 1 mA causing slight muscle contraction.ZnPP 50 μmol/kg was intraperitoneally injected at 12 h before each stimulation in LPS+ EA+ ZnPP group, and the equal volume of normal saline was given instead in the other groups.After the end of EA stimulation on the last day, LPS 5 mg/kg was intraperitoneally injected to induce brain injury.Open field tests were performed at 1 day after LPS injection to record the number of rearing and amplitude of neuronal calcium signals during rearing.Novel object recognition tests were conducted at 3 days after LPS injection, and the exploration index and amplitude of neuronal calcium signals while exploring novel objects were recorded.The mice were sacrificed after the end of behavioral testing, and the brain tissues were obtained and stained by Nissl, and the neurons in the hippocampal CA1 region were counted. Results:Compared with group C, the number of rearing and amplitude of calcium signals in neurons in the hippocampal CA1 region during rearing were significantly decreased, the exploration index and amplitude of calcium signals in neurons in the hippocampal CA1 region while exploring novel objects were decreased, and the neuron counts were reduced in LPS, LPS+ EA and LPS+ EA+ ZnPP groups ( P<0.05 or 0.01). Compared with group LPS, the number of rearing and amplitude of calcium signals in neurons in the hippocampal CA1 region during rearing were significantly increased, and the exploration index and amplitude of calcium signals in neurons in the hippocampal CA1 region while exploring novel objects were increased in group LPS+ EA ( P<0.05), and no significant change was found in the parameters mentioned above in group LPS+ EA+ ZnPP ( P>0.05). Compared with group LPS+ EA, the number of rearing and amplitude of calcium signals in neurons in the hippocampal CA1 region during rearing were significantly decreased, and the exploration index and amplitude of calcium signals in neurons in the hippocampal CA1 region while exploring novel objects were decreased in group LPS+ EA+ ZnPP ( P<0.05). Conclusion:The mechanism by which EA reduces LPS-induced brain injury is related to the activation of the endogenous protective mechanism HO-1 in mice.