Mice have been widely used in the study of primary liver cancer owing to the close similarity of its genome to that of humans,its strong reproductive ability,the low cost of model construction,and the ease of genetic manipulation,including molecular mechanisms of pathogenesis and potential drug targets.Traditional animal models are increasingly falling short of meeting the needs of precision medicine research because of their inability to reproduce tumor microenvironment interactions and control the specificity of molecular subtypes.This study systematically compared the technical advantages of tail vein high-pressure injection,combined with transposon system(HTVI-TS),with traditional models in liver cancer research,and focused on the application value of the HTVI-TS model in the mechanism study of tumorigenesis and development,immunotherapy response prediction,and individualized evaluation of targeted drugs.This report presents a new research platform for precise diagnosis and treatment of primary liver cancer by simulating the heterogeneous evolution process of the cancer.The findings provide a theoretical basis for optimizing the selection of preclinical research models for liver cancer;the expansion potential of this technology in liver cancer research is outlined.

Mice have been widely used in the study of primary liver cancer owing to the close similarity of its genome to that of humans,its strong reproductive ability,the low cost of model construction,and the ease of genetic manipulation,including molecular mechanisms of pathogenesis and potential drug targets.Traditional animal models are increasingly falling short of meeting the needs of precision medicine research because of their inability to reproduce tumor microenvironment interactions and control the specificity of molecular subtypes.This study systematically compared the technical advantages of tail vein high-pressure injection,combined with transposon system(HTVI-TS),with traditional models in liver cancer research,and focused on the application value of the HTVI-TS model in the mechanism study of tumorigenesis and development,immunotherapy response prediction,and individualized evaluation of targeted drugs.This report presents a new research platform for precise diagnosis and treatment of primary liver cancer by simulating the heterogeneous evolution process of the cancer.The findings provide a theoretical basis for optimizing the selection of preclinical research models for liver cancer;the expansion potential of this technology in liver cancer research is outlined.

Objective:To provide data support for acquired immunodeficiency syndrome (AIDS) clinical treatment by evaluating the antiviral therapy effect of integrase inhibitors (INIs) and analyzing the drug resistant mutations.Methods:Patients who exposed to INIs more than 1 year were analyzed retrospectively. Virus suppression failure subjects(viral load ≥1 000 copies/ml) were sequenced for drug resistance analysis.Results:Of 408 patients, 12 cases(2.9%) were virologic failure, 8 cases had drug resistance mutations. The proportion of drug resistance was 2.0%(8/408). Among them, only 1 case(0.2%, 1/408) was resistant to INIs with associated mutations: T66I, G118R and E138K; 7 cases(1.7%, 7/408) were resistant to nucleoside reverse transcriptase inhibitors(NRTIs) with major mutations: M184V/I, D67N for NRTIs; 5 cases(1.2%, 5/408) were resistant to non-nucleoside reverse transcriptase inhibitors(NNRTIs) with major mutation: K103N; 1 case(0.2%, 1/408) was resistant to protein inhibitors (PIs), and associated mutations was I50L.1 case was resistant simultaneously to INIs, NRTIs and NNRTIs, Dual-class mutations were observed in 4 cases(3 cases to NRTIs and NNRTIs, 1 case to PIs and NNRTIs).Conclusions:The study result showed that the drug resistance rate of INIs was low in Hunan province, however, the INIs drug resistance surveillance was necessary.

Objective:To understand the status of HIV-2 infection and the epidemiological characteristics of HIV-2 infected individuals in Hunan province.Methods:The stock blood samples with HIV-2 indicative bands in the original records of 15 AIDS confirmation laboratories in Hunan province from 2003 to 2020 were collected. The samples were tested by Mikrogen GmbH (HIV 1+ 2) antibody comfirmatory kit (Germany). And meanwhile the epidemiological data of the first HIV test and the epidemiological follow-up records of the cases who could be contacted were collected.Results:A total of 378 samples with HIV-2 indicative bands were collected, involving 363 individuals. Serological test result showed that 326 cases (89.81%) were HIV-1 antibody positive, 18 cases (4.96%) were HIV-2 antibody positive, 12 cases (3.31%) were HIV antibody positive but could not be typed, 6 cases (1.65%) were HIV antibody uncertain and 1 case (0.28%) was negative for HIV-1/2 antibody. There were 15 cases from Xiangtan city and the other 3 cases from Changsha city among the 18 HIV-2 antibody positive individuals. The result of epidemiological investigation showed that there were 12 males (66.67%) and 6 females (33.33%), with a male-to-female ratio of 2∶1. The average age of the first detection was (56.94±12.52) years, in the males the age ranged from 33 to 76 years and in the females the age ranged from 44 to 66 years. The male age span was larger than that of the female. There were 10 married cases (55.56%) including one couple, 6 divorced or widowed cases (33.33%), 2 cases (11.11%) with unknown marital status. There were 13 cases from hospital monitoring (72.22%), 2 cases each from prison detention and blood screening in volunteer donors (22.22%), and 1 case from spouse screening (5.56%). These samples were tested for the first time in 2005, 2009, 2013, 2014, 2018, and 2020, with 1 case each, 6 cases in 2016, 2 cases in 2017, and 4 cases in 2019. By the end of 2020, 9 cases were alive and 9 cases were dead or missing. Three cases have accepted antiviral treatment. Of the 7 cases that could be followed up, all admitted heterosexual transmission, 6 cases denied any history of traveling abroad, and 1 case denied any history of foreign sexual intercourse.Conclusions:HIV-2 epidemic has lasted for a long time in Hunan province, local infection is not an occasional case, and there is a possibility of long-term clustering epidemic spread. This suggests that the country should strengthen the surveillance, detection, diagnosis and treatment of HIV-2 research and pay attention to the risk of HIV-2 transmission.

Objective To evaluate the safety and efficacy of mechanical thrombectomy in treating in-stent restenosis of lower extremity arteriosclerosis obliterans. Methods From May 2015 to Sep 2016, the clinical data of 9 cases of lower extremity arteriosclerosis obliterans who were with in-stent restenosis(3 were stent graft)were retrospectively collected, and of which 7 were males and 2 were females with a mean age of (75.4 ± 6.3)years old. All the cases were treated by mechanical thrombectomy of Rotarex catheter. All the patients were diagnosed via low-extremity artery CTA, and treated by means of the Rotarex catheter, combined with angioplasty and stent if necessary. All patients received antiplatelet therapy. Doppler ultrasonography was taken during the followed-up. Results All the 9 cases were successed in technology, without complications in hospital. All patients received Rotarex mechanical thrombectomy. Six of which used balloon and 1 stent implanted. The ABI increased from 0.29 ± 0.07 to 0.88 ± 0.07 after treatment, the difference was statistically significant(t=28.875,P<0.05). All the patients were followed up for 3—18 (median time, 11.5)months. No death and symptoms recurrence appeared during the follow-up. Conclusions Mechanical thrombectomy using Rotarex catheter is a safe and effective treatment for in-stent restenosis in lower extremity arterial diseases.

Objective To explore the security and the short term efficacy of VIABAHN stents in the treatment of branching area lesions in lower extremity arterial diseases. Methods The data of 16 patients (11 male and 5 female, aged 59.0 to 81.0 with median of 71.6) with lower extremity arterial occlusive disease from November 2014 to June 2015 were analyzed retrospectively. All lesions were located around the branching area of the lower extremity artery (3 cases in the internal iliac artery orifice, 6 cases in the deep femoral artery orifice and 7 cases in the vascular net around the knee). The short?term effects on these patients in the follow-up period, such as the success rate of surgical technique, the improvement of symptoms and the incidence of complications were summarized. Results Revascularization was technically successful in all 16 patients, and ischemic symptoms relieved significantly after the operation. The ABI were 0.36±0.12 before and 0.89±0.10 after the operation. The patients were followed up for 3 to 9 months (median 5.5 months). All the patients were achieved limb salvage and no complication occurred. Conclusions VIABAHN stent is safe and effective for the treatment of lower extremity arterial occlusive disease. The branches around the lesion can be covered with VIABAHN stents.

OBJECTIVETo determine the prevalence rates of nucleotide reverse-transcriptase inhibitor (NRTI) and nonnucleoside reverse transcriptase inhibitor (NNRTI)TDRs among HIV-1 ART-naїve patients in Hunan province using the ultra deep sequencing (UDS) technique.

METHODSART-naїve subjects diagnosed in Hunan between 2010 and 2011 were evaluated by both UDS technique and Sanger sequencing techniques, to the 1% variant level. Mutations were scored using the Stanford HIVdb algorithm to infer the status on drug resistance.

RESULTSUDS method was performed on 90 ART-naїve subjects that seeking service of care, in Hunan. In total, 42.2% (38/90) of the subjects showed major NRTI or nonnucleoside reverse transcriptase inhibitor NNRTI TDRs by UDS technique, at a HIV variant frequency level of ≥1%, 15.6% (14/90) showed NRTI TDR, 16.7% (15/90) showed a major NNRTI TDR and 10% (9/90) were both resistant to NRTI and NNRTI when variants were analyzed by Stanford HIVdb.

CONCLUSIONART-naїve subjects from Hunan province, which had been predominately infected by subtype AE, would frequently possess HIV variants with NRTI/NNRTI TDRs that would affect the use of first line ART in the region, identified by the UDS technique. Further studies were needed to describe the prevalence of TDRs and to gather related information.

Anti-HIV Agents ; therapeutic use ; China ; Drug Resistance, Viral ; genetics ; HIV Infections ; drug therapy ; virology ; HIV-1 ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Prevalence ; Reverse Transcriptase Inhibitors ; analysis

Objective To determine the prevalence rates of nucleotide reverse-transcriptase inhibitor (NRTI) and nonnucleoside reverse transcriptase inhibitor (NNRTI) TDRs among HIV-1 ART-na?ve patients in Hunan province using the ultra deep sequencing(UDS) technique. Methods ART-na?ve subjects diagnosed in Hunan between 2010 and 2011 were evaluated by both UDS technique and Sanger sequencing techniques,to the 1%variant level. Mutations were scored using the Stanford HIVdb algorithm to infer the status on drug resistance. Results UDS method was performed on 90 ART-na?ve subjects that seeking service of care,in Hunan. In total,42.2%(38/90)of the subjects showed major NRTI or nonnucleoside reverse transcriptase inhibitor NNRTI TDRs by UDS technique,at a HIV variant frequency level of≥1%,15.6%(14/90)showed NRTI TDR,16.7%(15/90) showed a major NNRTI TDR and 10%(9/90)were both resistant to NRTI and NNRTI when variants were analyzed by Stanford HIVdb. Conclusion ART-na?ve subjects from Hunan province, which had been predominately infected by subtype AE,would frequently possess HIV variants with NRTI/NNRTI TDRs that would affect the use of first line ART in the region,identified by the UDS technique. Further studies were needed to describe the prevalence of TDRs and to gather related information.