Objective To explore the research hotspots and trends in the field of CSCs through the bibliometric analysis of the literature on CSCs. Methods Based on the core database of Web of Science, CiteSpace was used to analyze the annual distribution of published articles, authors, institutions, countries, journals, citations and keywords, and to explore the frequency, centrality and clustering of key words. Results (1) A total of 8131 articles were included after screening. China was the country with the largest number of articles, and Sun Yat-Sen University was the organization with the largest number of articles; (2) The hot spots in the field of CSCs are the research of CSCs in breast cancer and pancreatic cancer, the research of CSCs sorting and identification of molecular markers ALDH and genes PTEN, Sox2, C-myc, EZH2, the mechanism of EMT inducing the production of CSCs and promoting tumor metastasis, cellular and molecular mechanisms of CSCs resistance to chemical, radiation and targeted drug attacks, Wnt/β-catenin signaling pathway and tumor microenvironment regulate the differentiation of CSCs and targeted inhibition of CSCs in the treatment of malignant tumors; (3) The research trend of CSCs is CSCs stem research-biological mechanism of CSCs-CSCs application in the treatment of cancer. Conclusion The focus and direction of CSCs research are EMT inducing CSCs to promote tumor metastasis, CSCs resisting chemical attack, mesenchymal stem cells regulating CSCs, the metabolism of CSCs, and inhibitors targeting CSCs at present and in the future.

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.

Objective To investigate the research hotspots and trends in the field of immunotherapy for liver cancer in 2011-2020 based on bibliometric methods. Methods The Web of Science-SCI Expanded database was searched with the following search strategy: #1 TS = (Liver Neoplasms OR Neoplasms, Hepatic OR Neoplasms, Liver OR Liver Neoplasm OR Neoplasm, Liver OR Hepatic Neoplasms OR Hepatic Neoplasm OR Neoplasm, Hepatic OR Cancer of Liver OR Hepatocellular Cancer OR Cancers, Hepatocellular OR Hepatocellular Cancers OR Hepatic Cancer OR Cancer, Hepatic OR Cancers, Hepatic OR Hepatic Cancers OR Liver Cancer OR Cancer, Liver OR Cancers, Liver OR Liver Cancers OR Cancer of the Liver OR Cancer, Hepatocellular) AND #2 TS = (Immunotherapy OR Immunotherapies OR Immunity therapy); time span: 2011-2020; type of literature: Article; language: English. CiteSpace software was used to perform a visualized analysis of the articles in the field of immunotherapy for liver cancer published in 2011-2020 from the aspects of the distributions of year, country, institution, author, journal, and fund, times cited, and keywords, and the frequency, centrality, and clustering of keywords were discussed. Results A total of 1972 articles on immunotherapy for liver cancer were included, and the analysis showed that China was the country with the largest number of articles, Sun Yat-sen University was the institution with the largest number of articles, and Journal for Immunotherapy of Cancer was the journal with the largest number of articles. The research hotspots in this field included tumor-associated macrophages, oncolytic virus (such as adenovirus), tumor vaccine therapy, adoptive cellular immunotherapy, immune checkpoint inhibitors, and combined immunotherapy. The trend of this field was tumor vaccine therapy → immunotherapy for oncolytic virus → adoptive cellular immunotherapy → immune checkpoint inhibitor therapy. Conclusion Immunotherapy for liver cancer has undergone continuous development in the recent ten years, and with the research and development of tumor vaccine therapy, oncolytic virus, and immune checkpoint inhibitors and the improvement of immune checkpoint inhibitors, combined treatment based on immunotherapy is expected to further improve the clinical outcome of liver cancer.

Objective:To detect the genes of common genetic diseases in newborns with the high-throughput sequencing technology based on target gene capture, to study the incidence rate of such diseases, the carrying rate and variant types of pathogenic mutations related to such diseases, and to explore the application value of the high-throughput sequencing technology in screening genetic diseases of newborns.Methods:The heel blood of 1 793 newborns born in Guangdong province from June 2019 to April 2020 were collected, and the exon regions of 138 common genetic disease-related genes in neonates were detected using the high-throughput sequencing technology based on target gene capture.The pathogenicity of the mutations was interpreted according to the " Classification Criteria and Guidelines for Genetic Variation(2017)" , in which known disease and probable disease were considered as positive mutations.The positive mutations were verified by Sanger sequencing technology, and the test results were analyzed with statistical methods.Results:Among the 1 793 newborns, 978 were male and 815 were female.A total of 158 positive cases were screened(8.81%), and 11 positive diseases were detected.Among the positive diseases, there were 41 cases(2.29%)of autosomal recessive deafness type 1A, 40 cases(2.23%)of Gilbert syndrome or Crigler-Najjar syndrome, and 33 cases(1.84%)of glucose-6-phosphate dehydrogenase deficiency(1.84%), 19 cases(1.06%)of familial hypercho-lesterolemia, 18 cases(1.00%) of sodium taurocholate cotransporter peptide deficiency disease, 2 cases(0.11%)of mitochondrial non-syndromic deafness, 2 cases(0.11%)of Citrin deficiency, 1 case(0.06%)of holocarboxylase synthase deficiency, 1 case(0.06%)of β-thalassemia and 1 case(0.06%)of metachromatic leukodystrophies.Of all studied cases, 972 carried one or more positive mutations, involving 85 kinds of diseases in total.The diseases with a high carrying rate were Gilbert syndrome or Crigler-Najjar syndrome(359 cases, 20.02%), autosomal recessive deafness type 1A(302 cases, 16.84%), and sodium taurocholate cotransport peptide deficiency disease(291 cases, 16.22%). The high-frequency mutation sites were UGT1A1 gene c. 211G> A, GJB2 gene c .109G> A and SLC10A1 gene c. 800C> T. Conclusions:The common genetic diseases detected in neonates from Guangdong province are autosomal recessive deafness type 1A, Gilbert syndrome or Crigler-Najjar syndrome, glucose-6-phosphate dehydrogenase deficiency, familial hypercholesterolemia, and sodium taurocholate cotransport peptide deficiency.There are high-frequency carrying mutation sites in the population.Preliminary genetic screening of common neonatal genetic diseases can accumulate data and experience for the development of newborn genetic screening.

Objective: To evaluate the risk factors of hypercoagulability in the patients with chronic kidney disease (CKD) by thrombelastograph.Methods:According to the maximal elasticity of thrombus(MA),221 patients with chronic kidney disease under-going thromboelastography were divided into two groups: low coagulation group (MA<69mm, n=139) and high coagulation group (MA≥69mm,n=82). The basic conditions of the two groups were analyzed respectively, including gender, age, height, weight, concomitant diseases such as diabetes mellitus,hyperlipidemia and nephrotic syndrome,medication situation such as recombinant hu-man erythropoietin,anti-platelet drugs and hormones,renal function such as CKD1-3 stages and CKD4-5 stages,clotting parameter re-sponse time(R value),clotting time(K value),angle α,maximum thrombus(MA)and the other coagulation-related indicators such as platelet PLT,and binary logistic regression was used to analyze the risk factors causing hypercoagulability. Results:There were no significant differences in age,gender,height and weight etc(P>0.05)while there were significant differences in concomitant diseases, drug use,renal function, coagulation indicators including thrombus elasticity and blood index between the groups (P<0.05). The risk factors of hypercoagulation mainly included disease factors (diabetes OR 1.895,95% CI 1.082-3.318, nephrotic syndrome OR 2.501,95% CI 1.429-4.379,CKD4-5 stage OR 1.989,95% CI 1.136-3.483),and drug factors(recombinant human erythropoietin rHuEPO)(OR 2.254,95% CI 1.207-4.208). Conclusion: In the patients with CKD, diabetes mellitus, nephrotic syndrome and CKD4-5 stages increase the hypercoagulability of patients,and rHuEPO also increases the risk of hypercoagulability in the patients with renal anemia.

Objective: To investigate the application value of thrombelastography(TEG) in coagulation monitoring for ACS patients.Methods: Totally 255 ACS patients were selected with coagulation monitoring by TEG.The patients were divided into none ST-segment elevation myocardial infarction (NSTEMI) group and ST-segment elevation myocardial infarction (STEMI) group.The clotting characteristics in different types of ACS patients were compared and analyzed.Results: The ACS patients had higher intensity of thrombosis (MA) and Angle value.D-dimer and MA were significantly different between NSTEMI group and STEMI group(P＜0.01).The drug utilization in STEMI group was closer to the requirements of the guidelines.Conclusion: TEG shows high application value in coagulation monitoring for ACS patients.MA value and Angle value are more sensitive in evaluating hypercoaguable state.

Objective To explore the diagnosis and treatment of biotinase deficiency (BTD) manifested as encephalomyelopathy.Methods The clinical data of one child with BTD were retrospectively analyzed.The pertinent literatures were reviewed.Results A six-year-old male child suffered from progressive spastic paralysis of lower limbs for 3 months before admission.A similar symptoms occurred after a cold in 3-year-old.It was easy to peel skin on her hands and she had angular stomatitis.Audio visual evoked potential was detected to be abnormal in other hospital.After hospitalizion,the cerebrospinal fluid examination was normal,and MRI showed long T1 long T2 signals bilateral occipital lobe and basal ganglia region.Because the child represented medulla palsy,and so the tracheal intubation ventilator was administrated to assist ventilation.Urine gas chromatography/mass spectrometry (GC/MS) analysis showed increases of lactic acid,3-hydroxy acid,3-tiglyl glycine,methylcitric acid,and ethylene lactic acid.Serum MS/MS analysis showed that the concentrations of propionyl camitine and 3-hydroxyisovaleryl carnitine were increase obviously.The serum biotinase level was significantly decrease to 0.076 pmol/(min·mm3).The diagnosis of BTD was confirmed.After supplementation biotin,40 mg/d,the ventilator was successfully weaned on the third day,the child walked again after 2 weeks,and the rash was vanished.After 3 weeks,the head MRI showed disappearance of the original lesion,and there was no abnormal in spinal cord.The BTD gene detected by PCR direct sequencing showed a heterozygosis mutation of T172T/C in the second exon and a homozygous mutation of T1413C in the fourth exon,which was confirmed as a pathogenic mutation by pedigree verification and database query.After discharge,the oral administration of biotin 20 mg/d continued,and no abnormality was found in 2 years of follow-up.Conclusions The manifestations of BTD are complex and diverse.The analysis of urine GC/MS and serum MS/MS can assist the diagnosis.The determination of biotinase activity and gene detection of BTD can further confirm the diagnosis.Timely biotin supplementation has significant treatment efficacy.

Objective To explore the clinical,radiological and gene mutation features ofERCC8 gene in one patient with Cockayne syndrome.Methods Clinical and radiological data of a girl diagnosed with Cockayne syndrome through gene detection were retrospectively analyzed.Next-generation sequencing was used to detect genetic cause.Sanger sequencing was used to confirm the candidate variants and detect mutations in her parents and sister.ResuRs The patient showed psychomotor retardation,growth failure,special face,and light sensitivity.Neurological examination revealed noticeable developmental delay,motor impairment,spastic paralysis,and cerebellar ataxia.Brain MRI revealed symmetrical demyelination of bilateral centrum semiovale and periventricular white matter.The cerebellum was atrophic.The patient was found to have compound heterozygous mutations of c.397C＞T(p.Q133X) and c.394_398del(p.L132fs).Sanger sequencing showed these two mutations were inherited from her mother and father respectively.Conclusions Next-generation sequencing technology is a useful tool for the detection of mutation in ERCC8 gene,which is valuable for the diagnosis of Cockayne syndrome.These two mutations expanded the mutation spectrum of Cockayne syndrome in Chinese population.

Objects To investigate the correlation of the single nucleotide polymorphism ( SNP) of clopidogrel related gene CYP2C19, ABCB1, PON1 to the occurrence of clopidogrel resistance ( CR) and TEG among patients after percutaneous coronary intervention.Methods A total of 299 patients after PCI were enrolled from April 2015 to December 2015.It genotyped the CYP2C19(rs4244285,rs4986893)ABCB1 ( rs1045642 ) and PON1 ( rs662 ) gene, measured clopidogrel response by TEG.Accordingly, all the enrolled 299 patients were then divided into CR group (n=17) +non-CR (NCR) group (n=282) or CLR group (n=54) +non-CR (NCR) group (n=245) by TEG(%).All the patients were divided into EM、IM and PM group by CYP2C19 genotype.The age of patient in CR (71.1 ±11.1) years old is higher than NCR (65.02 ±10.51) years old (t=2.559, P<0.05).Results CYP2C19 PM was associated with decreased of TEG(ADP) (Z=-2.065, P=0.039), while it was not related to the age of patient(Z=0.405,P>0.05).There was no significant difference between CR(χ2 =0.175,P=0.916) CLR(χ2 =1.589,P=0.452)and the level of TEG(ADP) (Z=-0.030,P=0.976) in PON1(rs662) polymorphism.There was no significant difference between CR(χ2 =1.722,P=0.423) CLR(χ2 =0.176,P=0.916) and the level of TEG(ADP) (Z=-0.331,P=0.741) in ABCB1(rs1045642) polymorphism.Conclusions CYP2C19 PM is associated with decreased of TEG(ADP).It is considered that no correlation exists between ABCB1(rs1045642) and PON1(rs662) polymorphism and clopidogrel resistance in patients with coronary heart diseases.The loss of function of ABCB1 ( rs1045642 ) and PON1 ( rs662 ) is not associated with decreased of TEG(ADP) in CYP2C19 PM patients.

Delphi method is a kind of forecasting method with several rounds of consultation with experts. It has three major characteristics including anonymity,information feedback and statistical analysis of results. With the continuous development of the method,its application fields is widened from the initial development of sociology to clinical medicine,psychology,nursing and so on. Since pharmacy and clinical medicine is inseparable,Delphi method used in pharmacy field has become the new direction of pharmaceutical research,and it can provide a new method for the pharmaceutical regulations,medical risk assessment and development of clinical pharmacy. In the paper,the application of Delphi method in the field of pharmacy was summarized in order to provide new ideas for the development of pharmacy.