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.

After being treated with acupuncture, some patients with idiopathic tinnitus may experience a short-term aggravation of tinnitus symptoms on the original basis. These symptoms can be gradually relieved and the overall condition fluctuates towards recovery. This phenomenon has brought some difficulties to patients and clinicians. Based on the academic view of TCM, "destroying pathogens and re-building balance", and in association with the existing understanding of acupuncture in modern medicine for tinnitus, this paper briefly discusses the mechanism and influencing factors of symptom fluctuation in patients with idiopathic tinnitus after acupuncture treatment in terms of both TCM and modern medicine, and proposes the future direction in the research of symptom fluctuation, so as to promote the recognition of clinicians and patients on symptom fluctuation and make rational use of its positive effects. Besides, it is hoped that more researchers will pay attention to symptom fluctuation and advance the exploration of it in academic field.
Humans ; Tinnitus/physiopathology* ; Acupuncture Therapy ; Male ; Female

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.

Drosophila neural development undergoes extensive chromatin remodeling and precise epigenetic regulation. However, the roles of chromatin remodeling in establishment and maintenance of cell identity during cell fate transition remain enigmatic. Here, we compared the changes in gene expression, as well as the dynamics of nucleosome positioning and key histone modifications between the four major neural cell types during Drosophila neural development. We find that the neural progenitors can be separated from the terminally differentiated cells based on their gene expression profiles, whereas nucleosome distribution in the flanking regions of transcription start sites fails to identify the relationships between the progenitors and the differentiated cells. H3K27me3 signal in promoters and enhancers can not only distinguish the progenitors from the differentiated cells but also identify the differentiation path of the neural stem cells (NSCs) to the intermediate progenitor cells to the glial cells. In contrast, H3K9ac signal fails to identify the differentiation path, although it activates distinct sets of genes with neuron-specific and glia-related functions during the differentiation of the NSCs into neurons and glia, respectively. Together, our study provides novel insights into the crucial roles of chromatin remodeling in determining cell type during Drosophila neural development.

Objective To investigate the clinical value of CT lymphangiography (CTL) combined with direct lymphangiography (DLG) in primary intestinal lymphangiectasia (PIL). Methods Sixteen patients diagnosed as PIL with intestinal enteroscopy were recruited in this retrospective study. All the patients were performed DLG and CTL one week before exploratory laparotomy. Subjective assessment in DLG included weak lymphatic fluid drainage, lymphangiectasia, lymphatic reflux, fistula and thoracic outlet reflux or obstruction. While for CTL combined with DLG, the intestinal and extra-intestinal lesions were evaluated, including lymph node, edema, lymphangiectasia and abnormal distribution, fistula, and lymphangiomatosis. All the diagnosis was compared with intestinal endoscopy results. Results For DLG, 16 weak lymphatic fluid drainages, 9 lymphangiectasia, 1 fistula with abdomen and 14 thoracic outlets weak lymphatic fluid drainage or obstruction were found. For DLG combined with CTL, 16 intestinal lumens dilatation and 14 circumferential intestinal thickening were found in intestinal lesions. While for extra-intestinal lesions, the imaging features included edematous findings (12 in mesentery, 7 ascites only, 2 hydrothorax and ascites, and 3 pericardial, thoracic and abdominal effusions), abdominal lymph nodes (6 cases), lymphangiectasia and abnormal distributions (14 cases), fistulas (lymph-intestinal luminal fistula in 4 cases, and lymph-abdominal fistula in 3 cases), lymphangiomatosis (3 cases), and thoracic duct outlet dysfunction and reflux (14 cases).The number of cases diagnosed as intestinal lymphangiectasia, intestinal luminal lymph exudation and lymph fistula were 16, 10 and 6 with intestinal endoscopy, while the number were 11, 0, and 4 with CTL combination with DLG. Conclusion Combination of CTL with DLG is valuable in the diagnosis of PIL.

Objective To evaluate the value of imaging examinations in the treatment of lymphangioleiomyomatosis (LAM) with chylothorax by thoracic duct extremity exploration.Methods Data of 34 LAM with chylothorax confirmed by pathology and clinical diagnosis were retrospectively analyzed.All patients underwent 99Tcm-DX lymphoscintigraphy and CT lymphangiography (CTL).Thoracic duct lesion types of 99Tcm-DX lymphoscintigraphy were type Ⅰ (abnormal concentration pattern),type Ⅱ (ectopic drainage pattern),and type Ⅲ (without image or transient image pattern).The type Ⅰ and type Ⅱ were diagnosed as thoracic duct abnormalities.Thoracic duct lesion types of CTL were type Ⅰ (dilatation pattern),type Ⅱ (distal obstruction pattern),type l (truck constriction pattern),type Ⅳ (ectopic drainage pattern),and type Ⅴ (no-display pattern).Type Ⅰ-Ⅳ were diagnosed as thoracic duct abnormalities.Consistency of displaying thoracic duct abnormalities between 99Tcm-DX lymphoscintigraphy and CTL was evaluated.Results The thoracic duct abnormalities in 99Tcm-DX lymphoscintigraphy were 58.82％ (20/34;type Ⅰ in 17,type Ⅱ in 3,type Ⅲ in 14),and in CTL were 73.53％ (25/34;type Ⅰ in 15,type Ⅱ in 3,type Ⅲ in 5,type Ⅳ in 2,type Ⅴ in 9).The consistency of CTL and 99Tcm-DX lymphoscintigraphy for detecting thoracic duct abnormalities was good (Kappa=0.679).In CTL thoracic duct types,type Ⅰ and Ⅱ were operated by thoracic duct-venous anastomosis or thoracic duct extremity release operation,type Ⅲ was operated by thoracic duct adhesion or compression band release operation,operative approach and method were chosen according to the abnormal thoracic duct flow path in type Ⅳ,type Ⅴ was took conservative treatment.Conclusion CTL is superior to 99Tcm-DX lymphoscintigraphy,which can clearly display the type of thoracic duct lesion and provide imaging informations to choose operation methods in thoracic duct exploration treatment for LAM with chylothorax.

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.