Transjugular intrahepatic portosystemic shunt （TIPS） is currently an effective procedure for the complications of portal hypertension. In recent years， rapid progress has been made in the field of TIPS in terms of technical approaches， prognostic models， and an expanding range of indications. The EASL recently issued the clinical practice guidelines on TIPS to comprehensively address all aspects of TIPS in patients with liver cirrhosis. This article makes an excerpt of the key recommendations in the guidelines.

Alzheimer's disease (AD) is regarded as a neurodegenerative disease, and it has been proposed that AD may be a systemic disease. Studies have reported associations between non-neurological diseases and AD. The correlations between AD pathology and systemic (non-neurological) pathological changes are intricate, and the mechanisms underlying these correlations and their causality are unclear. In this article, we review the association between AD and disorders of other systems. In addition, we summarize the possible mechanisms associated with AD and disorders of other systems, mainly from the perspective of AD pathology. Regarding the relationship between AD and systemic pathological changes, we aim to provide a new outlook on the early warning signs and treatment of AD, such as establishing a diagnostic and screening system based on more accessible peripheral samples.
Alzheimer Disease/therapy* ; Humans ; Brain/pathology*

Transarterial chemoembolization （TACE） is currently the primary treatment method for advanced liver cancer. This article elaborates on the current status of application of TACE in hepatocellular carcinoma from the aspects of existing techniques， patient selection， and efficacy assessment and summarizes the research advances and prospects of TACE combined with local treatment and systemic therapy， so as to provide new ideas for clinical practice and experimental studies.

ObjectiveTo evaluate the efficacy and safety of first-line transcatheter arterial chemoembolization （TACE） combined with targeted therapy and immunotherapy in the treatment of patients with stage Ⅱb/Ⅲa hepatocellular carcinoma （HCC） based on China Liver Cancer Staging （CNLC）. MethodsA total of 198 patients who received first-line TACE combined with targeted therapy and immunotherapy or received TACE alone from January 2015 to December 2022 in the First Affiliated Hospital of Soochow University were enrolled in this study， and after propensity score matching， there were 50 patients in combination group and 50 patients in TACE group. The Kaplan-Meier method was used to calculate median overall survival （mOS） and median progression-free survival （mPFS）. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate objective response rate （ORR） and disease control rate （DCR）， and Common Terminology Criteria for Adverse Events v5.0 was used to evaluate adverse events. The chi-square test was used for comparison of categorical data between two groups； the t-test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to estimate survival time and calculate 95% confidence interval （CI）， and the Log-rank test was used for comparison of mOS and mPFS between two groups. ResultsThe combination group had an mOS of 30.1 months （95%CI： 21.9‍ ‍—‍ ‍38.3）， and the TACE group had an mOS of 14.5 months （95%CI： 11.0 ‍—‍‍ ‍18.0）， with a significant difference between the two groups （χ²=17.8， P<0.001）； the combination group had an mPFS of 10.3 months （95%CI： 8.8‍ ‍—‍ ‍11.8）， and the TACE group had an mPFS of 7.1 months （95%CI： 5.8‍ — ‍8.4）， with a significant difference between the two groups （χ²=10.4， P<0.001）. There were significant differences between the combination group and the TACE group in ORR （84% vs 58%， P<0.05） and DCR （94% vs 80%， P<0.05）. There was no significant difference between the combination group and the TACE group in the incidence rate of adverse events （24% vs 16%， P=0.317）， and no adverse event-related deaths were observed in either group. ConclusionCompared with TACE alone， TACE combined with targeted therapy and immunotherapy has a better efficacy in the treatment of patients with CNLC stage Ⅱb/Ⅲa HCC， without increasing the incidence rate of severe adverse events.

Objective To detect and analyze the drug resistance characteristics,phylogenetic typing,and virulence gene distribution of Escherichia coli(E.coli)in blood culture.Methods The strains of E.coli isolated from consecutive non-repetitive blood cultures in our hospital from January 1,2019 to December 13,2020 were collected.The sensitivity of E.coli to 17 antibiotics was determined u-sing the micro-broth method.The bacterial genomic DNA was extracted using the boiling method,and then the arpA,chuA,yjaA,TspE4C2,ArpAgpE and trpAgpC genes were detected by PCR to determine the bacterial phylogroup.The virulence genes,including iutA,fimH,fyuA,kpsMT Ⅱ,cnf1,cvac,hlyA,traT,kpsMT Ⅲ,and PAI,were detected using the multiplex PCR.The differences in drug resistance and virulence gene distribution among different phylogroups were analyzed by the Chi-square test.Results 270 strains of E.coli in blood culture showed high resistance rates to ceftriaxone,compound sulfamethoxazole,ampicillin,ampicillin sulbactam,cefazolin,and ciprofloxacin,all exceeding 50.0％.They had good susceptibility to imipenem,ertapenem,amikacin,and piperacillin tazobactam,with resistance rates all below 5.0％.The most common phylogroups were types B2 and D,accounting for 38.0％and 16.2％,respectively,while type E and hidden branch type I were relatively rare,accounting for less than 1.0％.The virulence gene analysis revealed that the distribution rates of fimH and fyuA genes were the highest,both above 99.0％.The distribution rates of kpsMT Ⅲ,hlyA,and cvaC genes were relatively low,all below 20.0％.The Chi-square test showed that the distribution rates of viru-lence genes such as iutA,fimH,fyuA,kpsMT Ⅱ,cnf1,and PAI in the B2 group were significantly higher than those in the non-B2 group(P<0.05).The distribution rates of iutA,fyuA,kpsMT Ⅱ,cnf1,and PAI genes in the B2 group were significantly higher than those in the D group(P<0.05).Conclusion When treating bloodstream infections caused by E.coli,caution should be exercised in the use of drugs such as ceftriaxone,compound sulfamethoxazole,ampicillin,ampicillin sulbactam,cefazolin,and ciprofloxacin.When bloodstream infections are caused by phylogroup B2 E.coli,middle-stream urine culture should be performed simultaneously to confirm the source of infection and monitor the success rate of treatment.

Objective To evaluate the ability of average nucleotide identity(ANI)and 16S rDNA technology on the identification of Salmonella.Methods The genomes and corresponding serovars of global Salmonella were downloaded in batch from the GenBank database.The classical strains of Salmonella were used as typing strains.The ANI analysis was conducted by the fastANI software according to the silent parameters.The species and serovars of Salmonella were identified by their 16S rDNA using the online software SpeciesFinder.Results Among the downloaded 2 306 genomes,1 767 strains of Salmonella had 178 serovars,with 323 strains(18.3%)of Salmonella Typhimurium and 300 strains(17.0%)of Salmonella Enteritidis being the most common.The ANI analysis showed that with a 95%threshold,only 30 strains(1.3%)of Salmonella were assigned to a specific subspecies,while the remaining 2 276 strains(98.7%)of Salmonella could be assigned to 2-5 subspecies.When the threshold was 97%,all 2 306 strains(100%)of Salmonella could be assigned to a specific subspecies.Based on the analysis of 16S rDNA,only 1 072 strains(46.5%)of Salmonella were identified,of which 95.2%(1 021/1 072)of Salmonella subspecies were completely consistent with the results of ANI(≥97%)analysis.Only 2.4%(19/784)of Salmonella strains showed consistent results with known serovars.Conclusion ANI is more suitable for the identification of Salmonella species and subspecies,and ANI≥97%can be used as the identification standard for Salmonella subspecies.The sensitivity of 16S rDNA for the identification of Salmonella still needs to be improved.

Objective To analyze the epidemiological characteristics of mobile colistin resistance(mcr)genes in global Klebsiella pneumoniae(K.pneumoniae).Methods The genomes of K.pneumoniae were downloaded from the NCBI genome database by the As-pera software.After quality filtering using the CheckM v1.1.3 and Quest 5.0.2 software,the genomes were annotated using the Prokka v1.13.All the mcr gene sequences were downloaded from the NCBI website and a database was built using the makeblastdb command.Then,a self-made Perl script program was used to extract the nucleotide sequences of all genes from the annotation file as Query,and the local BLASTN analysis was performed to obtain mcr-positive strains.The gene sequence files and Profiles files of 7 housekeeping genes of K.pneumoniae were downloaded from the PubMLST website as the database,and the nucleotide sequences of the genes were extracted as Query using a self-made Perl script program.The local BLASTN analysis was implemented to determine the sequence type(ST)of each genome.Meta information of each strain,including isolation source,sample type,country,and date,were extracted in batch from the GenBank file of the downloaded K.pneumoniae genomes using a self-written Perl program to analyze the distribution characteristics of mcr-positive strains.The distribution differences of the mcr between different ST types were compared by the Chi-square test.Results Among the 11 429 global K.pneumoniae genomes included in this study,229 mcr genes were detected from 207 strains.Six variants of mcr were identified,mainly mcr-1(87/229,38.0％),mcr-8(59/229,25.8％),and mcr-9(59/229,25.8％).76 STs were identified from 207 strains,with ST15(21/207,10.1％),ST43(17/207,8.2％),ST11(16/207,7.7％),and ST 147(16/207,7.7％)being the predominant.Among 87 mcr-1 positive strains,31 STs were found,with ST43(17/87,19.5％)and ST15(10/87,11.5％)being the main ones.Among 59 mcr-8 positive strains,17 STs were identified,with ST43(17/59,28.8％)and ST11(9/59,15.3％)being the predominant.Among 59 mcr-9 positive strains,27 STs were detected,with ST147(11/59,18.6％)and ST274(11/59,18.6％)being the main ones.There were statistical differences in the variants of mcr genes carried by different ST types.The mcr-positive K.pneumoniae came from 28 countries across five continents worldwide,led by China(68/207,32.9％)and Thailand(45/207,21.7％),which were mainly from the human body(100/207,48.3％)and had a concentrated outbreak time from 2015 to 2018.Conclusion Among the global K.pneumoniae,the prevalence of mcr is mainly domina-ted by mcr-1,mcr-8,and mcr-9.The dominant clones of mcr-1 are mainly ST15 and ST43,while those of mcr-8 are mainly ST11 and ST43.The popularity of mcr-9 is mainly based on ST147 and ST274.Strengthening the monitoring of such bacteria may play an impor-tant role in preventing and controlling nosocomial infections.

Objective To analyze the prevalence and molecular characteristics of global Salmonella Typhimurium.Method The ge-nome and the corresponding serovars as well as meta-information of global Salmonella were downloaded in batch from the National Cen-ter for Biotechnology Information(NCBI)database using the online softwares,ResFinder,PlasmidFinder,Mobile Element Finder and MLST,to analyze the distribution of antibiotic resistant genes(ARGs),plasmids,mobile genetic elements(MGEs)and the sequence types(STs)among S.Typhimurium strains.Results A total of 101 ARGs were detected in 323 strains of S.Typhimurium,among which the most common was aac(6')-Iaa(322/323,99.69％),followed by sul2(155/323,47.99％),aph(3")-Ib(128/323,39.63％),aph(6)-Id(127/323,39.32％),tet(B)(109/323,33.75％),and blaTEM-1B(106/323,32.82％).Totally,36 plasmids were identified,among which IncFⅡ(S)(110/323,34.06％)and IncFⅠB(S)(108/323,33.44％)were the most common.Moreo-ver,376 MGEs were found,including 367 insertion sequences and nine transposons,among which MITEEc1(322/323,99.69％)and ISSen1(308/323,95.36％)were the most popular.Furthermore,323 strains of S.Typhimurium were assigned into 32 different STs,a-mong which,ST19(157/323,48.61％)and ST34(105/323,32.51％)were the most common accounting for over 82％.Among 115 strains of S.Typhimurium from human,18 STs were identified including ST19(52/115,45.22％)and ST34(39/115,33.91％)which were the most common.Conclusion S.Typhimurium carried multiple types of ARGs,in addition to the wide distribution of a large number of insertion sequences and plasmids,whch provide favorable conditions for the spread of drug resistance.Therefore,the meas-ures of prevention and control against the infection from this bacterium should be strengthened.

Objective:To investigate the safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia.Methods:Data of acute ischemic stroke patients with baseline National Institutes of Health Stroke Scale(NIHSS)score≤3 and a platelet count<100×109/L were obtained from a multicenter register.Those who required anticoagulation or had other contraindications to antiplatelet therapy were excluded.Short-term safety outcomes were in-hospital bleeding events,while the long-term safety outcome was a 1-year all-cause death.The short-term neurological outcomes were evaluated by modified Rankin scale(mRS)score at discharge.Results:A total of 1868 non-cardioembolic mild stroke patients with thrombocytopenia were enrolled.Multivariate regression analyses showed that mono-antiplatelet therapy significantly increased the proportion of mRS score of 0-1 at discharge(OR=1.657,95%CI:1.253-2.192,P<0.01)and did not increase the risk of intracranial hemorrhage(OR=2.359,95%CI:0.301-18.503,P>0.05),compared with those without antiplatelet therapy.However,dual-antiplatelet therapy did not bring more neurological benefits(OR=0.923,95%CI:0.690-1.234,P>0.05),but increased the risk of gastrointestinal bleeding(OR= 2.837,95%CI:1.311-6.136,P<0.01)compared with those with mono-antiplatelet therapy.For patients with platelet counts≤75×109/L and>90×109/L,antiplatelet therapy significantly improved neurological functional outcomes(both P<0.05).For those with platelet counts(>75-90)×109/L,antiplatelet therapy resulted in a significant improvement of 1-year survival(P<0.05).For patients even with concurrent coagulation abnormalities,mono-antiplatelet therapy did not increase the risk of various types of bleeding(all P>0.05)but improved neurological functional outcomes(all P<0.01).There was no significant difference in the occurrence of bleeding events,1-year all-cause mortality risk,and neurological functional outcomes between aspirin and clopidogrel(all P>0.05).Conclusions:For non-cardioembolic mild stroke patients with thrombocytopenia,antiplatelet therapy remains a reasonable choice.Mono-antiplatelet therapy has the same efficiency as dual-antiplatelet therapy in neurological outcome improvement with lower risk of gastrointestinal bleeding.