Objective:To analyze the influencing factors of genotypic drug resistance mutations in people living with human immunodeficiency virus and acquired immunodeficiency syndrome(PLWHA) who failed anti-retroviral therapy (ART) in Henan Province, in order to provide a basis for adjusting ART regimens and reducing drug resistance.Methods:PLWHA with virological failure (human immunodeficiency virus (HIV) RNA≥500 copies/mL) after receiving ART for more than 24 weeks were included in Henan Province from January 2018 to December 2022. Baseline CD4 + T lymphocyte counts, ART regimens and other clinical data were collected. HIV-1 gene subtypes and their drug resistance sequence mutations were detected in the Sixth People′s Hospital of Zhengzhou, and the sequences were submitted to the HIV Drug Resistance Interpretation System of Stanford University for comparison of test results. Genotypic drug resistance to nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI) and integrase inhibitors (INSTI) was determined. Multivariate logistic regression was used to analyze the influencing factors of drug resistance in patients with ART failure. Results:Among 982 PLWHA, the sequences of 899 cases were successfully amplified, and drug resistance was detected in 737 cases, with the drug resistance rate of 81.98%(737/899). The rates of resistance to NRTIs, NNRTIs, PIs and INSTIs were 71.97%(647/899), 79.31%(713/899), 5.23%(47/899) and 2.72%(20/734), respectively.The largest number of those who developed concomitant resistance to two classes of drugs was 588 cases (79.78%), mainly NRTI and NNRTI concomitant resistance in 583 cases (79.10%). There were 99 cases (13.43%) who developed resistance to only one class of drugs, and those who developed concurrent resistance to three classes of drugs were 48 cases (6.51%), and two cases (0.27%) were found to be resistant to all four classes of drugs mentioned above. A total of 10 HIV genotypes were detected, among which subtype B accounted for the most (59.73%(537/899)), followed by circulating recombinant form (CRF)01_AE subtype (21.91%(197/899)) and CRF07_BC subtype (9.45%(85/899)). The risk factors affecting the development of drug resistance were baseline CD4 + T lymphocyte counts, ART regimens and HIV-1 genotypes. The risk of drug resistance in patients with baseline CD4 + T lymphocyte counts <100/μL was 4.55 times (95% confidence interval ( CI) 2.69 to 7.70) higher than patients with CD4 + T lymphocyte counts≥250/μL, the risk of drug resistance in patients using 2NRTIs+ NNRTI regimen was 4.51 times (95% CI 1.75 to 11.63) higer than those using 2NRTIs+ INSTI regimen, and patients infected with B and CRF01_AE subtype was 2.18 times (95% CI 1.10 to 4.29) and 2.70 times (95% CI 1.26 to 5.78) higer than those with CRF07_BC subtype, respectively. Conclusions:The incidence of genotypic drug resistance in PLWHA with ART failure in Henan Province is high. Low baseline CD4 + T lymphocyte counts, 2NRTIs+ NNRTI regimens, and genotype B and CRF01_AE are risk factors for drug resistance in PLWHA.

Objective:To investigate the value of intratumoral and peritumoral radiomics features of multi-parameter MRI in evaluation of the status of human epithelial growth factor receptor 2 in breast cancer.Methods:The clinical, pathological and imaging data of 340 patients with pathologically confirmed breast cancer in Henan Provincial People′s Hospital from September 2019 to December 2020 were retrospectively collected. All patients were female, 48 (42, 55) years old. All patients underwent multi-parameter breast MRI before surgery, including dynamic contrast-enhanced T 1WI (DCE-T 1WI), fat-suppressed T 2WI (T 2WI) and diffusion-weighted imaging (DWI). The region of interest (ROI) for lesions were manually delineated and the segmented ROIs were zoomed in ring shape by 4 mm to acquire ROI intra and ROI prei, respectively. Then six sets of radiomics features were extracted from ROI intra and ROI prei of DCE-T 1WI, T 2WI and DWI. The cases were divided into a training set (272 cases) and a test set (68 cases) by stratified sampling at a ratio of 4∶1. The Mann-Whitney U test, Select K Best and minimum absolute contraction and selection operator were used for feature selection of the 6 sets of radiomics features. The feature subsets after reduction were used to construct independent and combined radiomics signatures with support vector machine algorithm to predict the HER2 status of breast cancer. Receiver operating characteristic curve was generated and area under curve (AUC) was calculated to compare the prediction performance of different models. Results:Of the 340 patients, 80 were HER2-positive and 260 were HER2-negative. Among the radiomics signatures based on single sequence, the DWI peri showed the best performance in predicting HER2 status of breast cancer, with an AUC of 0.678 for the test set. Among the combination of intratumoral and peritumoral radiomics signatures based on same sequence, the DWI intra+DWI peri had the highest prediction value, achieving an AUC of 0.774 for the testing set. Among the intratumoral or peritumoral radiomics signatures derived from two different sequences, the DCE-T 1WI intra+DWI intra and T 2WI peri+DWI peri showed the best predictive performance, yielding AUC of 0.766 and 0.769 in the testing set, respectively. Among the combination of intratumoral or peritumoral radiomics signatures derived from all 3 sequences or combinations of all features, the DCE-T 1WI intra+T 2WI intra+DWI intra+DCE-T 1WI peri+T 2WI peri+DWI peri obtained the highest prediction efficiency, with an AUC of 0.913 for the testing set. Conclusion:The radiomics features of intratumoral and peritumoral regions based on multi-parameter MRI have a certain value in non-invasive evaluation of HER2 status of breast cancer, which can help clinicians to provide scientific basis for decision-making of targeted therapy in patients with breast cancer.

Humans ; Mutation/genetics* ; HIV Infections/drug therapy* ; Drug Resistance ; Treatment Failure ; China ; Drug Resistance, Viral/genetics*

Objective:To analyze the drug resistance characteristics of HIV/AIDS patients in Henan Province with antiretroviral treatment (ART) failure through the genotypic drug resistance detection.Methods:Blood samples were collected from HIV/AIDS patients who received ART for more than 6 months with viral loads ≥1 000 copies/ml in 18 cities of Henan from January 2018 to May 2021. The genotypic drug resistance detection was conducted by using an In-house drug resistance detection method. The drug resistance mutation (DRM) and antiretroviral susceptibility were analyzed by submitting the determined sequences to the Stanford HIV-1 drug resistance database. The information about patients' demographic characteristics and antiviral treatment data were collected.Results:A total of 887 HIV/AIDS patients with ART failure, 812 sequences were successfully amplified with the success rate of 91.54%. In the 812 patients, 676 were drug resistant (83.25%, 676/812). The drug resistance ratesto nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) were 73.40% (596/812), 80.54% (654/812), 5.54% (45/812), and 2.56% (17/663), respectively. There were significant differences in drug resistance rates among four types of drugs ( χ2=1 686.34, P<0.001). The drug resistance rate to two drugs was 66.38% (539/812), and the drug resistance rate to three drugs was 5.79% (47/812). A total of 9 subtypes of HIV-1were detected, in which subtype B accounted for 59.61%(484/812), followed by subtype CRF01_AE (22.17%, 180/812) and subtype CRF07_BC (9.48%, 77/812). There were significant differences in drug resistance rate among different subtypes ( χ2=21.33, P=0.001). Among NRTIs related mutation sites, the DRM rate of M184V/I was highest (63.42%, 515/812), followed by K65R (27.46%, 223/812). The top three DRM rates were detected for K103N/S (34.98%, 284/812), G190A/S (26.11%, 212/812) and V106M/I (24.63%, 200/812) among NNRTIs related mutation sites, and M46I (4.31%, 35/812), V82A/F (3.82%, 31/812), and I54V/MV (3.69%, 30/812) among PIs related mutation sites. While among INSTIs related mutation sites, E157Q/EQ had the highest DRM rate (3.47%, 23/663), followed by R263K (0.75%, 5/663) and G140A (0.75%, 5/663). The resistance to lamivudine and emtricitabine of NRTIs was at high-level (65.52%, 532/812), and the resistance to nevirapine (77.46%, 629/812) and efavirenz (71.18%, 578/812) of NNRTIs was also at high-level. The medium/high-level resistance to lopinavir/ritonavir of PIs was only 4.19% (34/812), the medium/high-level resistance to elvitegravir and raltegravir of INSTIs was 1.66% (11/663) and 1.21% (8/663), respectively, and no high-level resistance to bictegravir or dolutegravir was found. Conclusions:The drug resistance in HIV/AIDS patients with ART failure was high in Henan, characterized by high drug resistance rates to NRTIs and NNRTIs, and diverse and complex resistance mutations. So high resistance barrier ART-regimens were recommended, and the viral load monitoring and drug resistance testing after ART should be strengthened.

Objective:To investigate the drug resistance of patients with acquired immunodeficiency syndrome (AIDS) who failed antiviral therapy.Methods:A total of 156 AIDS patients with antiviral therapy failure at the Sixth People′s Hospital of Zhengzhou from October 2017 to December 2018 were selected. The human immunodeficiency virus (HIV)-1 ViroSeq? genotyping method was used for the detection of HIV resistance, and Stanford University HIV drug resistance database (http: ∥hivdb.stanford.edu/) was used for testing results comparison.Results:Among the 156 AIDS patients with antiviral therapy failure, 122(78.21%) developed drug resistance. One hundred and six (67.95%) cases were multi-resistant to nucleoside reverse transcriptase inhibitor (NRTI), among which, 104 (66.67%) were resistant to lamivudine, emtricitabine and abacavir. One hundred and eighteen (75.64%) were resistant to non-nucleoside reverse transcriptase inhibitor (NNRTI), and 118 (75.64%) were multi-resistant to efavirenz and nevirapine. And seven (4.49%) were resistant to protease inhibitor (PI). There were 16 resistant sites for NRTI, with 87 (71.31%) most frequent M184V/I mutations. There were 13 resistant sites for NNRTI, with 49 (40.16%) K103N/R mutations. There were 11 resistant sites for PI, with 49 (40.16%) A71V/T mutations. The antiviral drugs lamivudine and emtricitabine were moderately and highly resistant in 102 (83.61%) cases, efavirenz and nevirapine were moderately and highly resistant in 117 (95.90%) cases. Once drug resistance developed, these drugs were likely to be moderate or high resistance. There were 29 (23.77%), 48 (39.34%), and five (4.10%) cases were resistant to zidovudine, tenofovir and lopinavir/ritonavir, respectively. The resistance barrier of these drugs was relatively high.Conclusion:The incidence of drug resistance in patients with AIDS treatment failure is high, and multi-drug resistance is serious with various sites of drug resistance.

Objective To investigate the expression and significance of NADPH oxidases Nox2 and Nox4 in mouse colitis. Methods Mouse colitis model was established by using six-to-eight-week-old 129S /SV mice. Mice were randomly divided into 3 groups: control group,1. 5％ dextran sulfate sodium (DSS) group and 3. 0％ DSS group (n = 10 for each group). All of them were fed for 7 days to adapt to the environment. After then,the control group was given drinking water only,colitis was induced by giving drinking water consisted of 1. 5％ DSS or 3. 0％ DSS for 6 days. Weight loss,disease activity index (DAI) and histology were used to quantify the severity of colon inflammation. Oxidative stress indicator,malondialdehyde (MDA) in serum was measured by biochemical methods. The mRNA levels of pro-inflammation cytokines (IL-1β,IL-6 and TNF-α) were quantified by real-time PCR. The protein and mRNA expression of Nox2 and Nox4 in colon tissue of mice was evaluated by immunohistochemistry and real-time PCR,respectively. Results There was no colitis in the control group,while mild and severe enteritis was found in mice in the 1. 5％ DSS group and 3. 0％ DSS group,respectively. The number of goblet cells was decreased significantly in the 1. 5％ DSS group than that of control group (P < 0. 05),and further reduced in the 3. 0％ DSS group (P < 0. 05). MDA was enhanced along with the increased concentration of DSS (P < 0. 05 for both). The expression of Nox2 and Nox4 protein and mRNA was different with the severity of inflammation. The expression of protein and mRNA of both Nox2 and Nox4 were increased in 1. 5％ DSS group compared with the control group (P < 0. 05),and further reduced in the 3. 0％ DSS group (P < 0. 05). Nox2 mostly expressed in the phagocytes and neutrophils; Nox4 mostly expressed in the neutrophils and lymphocytes. Conclusion Nox2 and Nox4 play an important role in the occurrence of mouse colitis.

Pace of life and work of people is accelerating nowadays, and hospitals keep improving their services, which gives rise to the decoction and delivery service from the third party vendors for traditional Chinese medicine(TCM).Given the quality control standards for the TCM decoction service as issued by Zhejiang and other regions, the systems of supervision and assessment remain incomplete.Authors of the paper introduced a project improvement team, composed of Chinese medicine pharmacy, Chinese medicine experience specialists, vendors of Chinese medicine decoction and express delivery companies, hence establishing a " three-in-one" supervision system of Internet+TCM decoction and delivery service. This practice can optimize the assessment indexes, strengthen the assessment system of assessment transformation and supervision system for patient medication.It proves that the practice contributes to higher quality and safety of TCM decoction and delivery service, improves the ability and level of TCM services, and ensures the medication safety of patients.

Objective To discuss the epidemiology and clinical characteristics of AIDS in some part of Henan regions.Methods Retrospective analysis was conducted based on the clinical and epidemic information collected from AIDS patients who were treated in the Sixth People's Hospital of Zhengzhou between 2006 and 2015 in He'nan province.Results Between 2006 and 2015,the number of hospitalization increased every year.The average growth rate was 20.31％.The average age of patients was (43.91 ± 13.56) years old.The patients from 40 to 60 years old group occupied 54.06％ of total patients,and 71.12％ of patients were farmers.During 2006 to 2015,the propagation path changed a lot.Before 2008,blood transmission was the major propagation path (72.72％),but after 2013,the major propagation path was sexual activity (59.69％).40.41％ of patients were infected by two or more opportunistic infections.The top five opportunistic infections were bacterial pneumonia (32.68％),tuberculosis (19.29％),fungal infection (18.65％),pneumocystis carinii pneumonia (12.96％),extra pulmonary tuberculosis (7.45％).The death rate was 5.79％.The number of CD4 cells in peripheral blood was closely related to the severity of illness.Conclusion Early anti-virus treatment and opportunistic infection control are key factors to relieve the severity of illness and reduce the death rate.

Objective To study the survival status and the prognostic factors of aquired immune deficiency syndrome (AIDS) patients under the highly active antiretroviral therapy (HAART) in He'nan Province.Methods Survival data of AIDS patients were collected from the National HAART reporting system between 2005 and 2015,and analyzed using SPSS 23.0 software.Results A total of 38 143 AIDS cases were enrolled in this study.The cumulative survival rate of patients under antiretroviral therapy after 1-5 years were 95％,91％,89％,86％ and 85％,respectively.The cumulative death cases were 5 704 and the total mortality was 3.68/100 person years (5 704/155 060 person years).A total of 1 975 cases died within a year with a percentage of 34.62％.Cox proportional hazard regression model analysis indicated that the hazard ratioc (HR [95％CI]) of death in patients with age of 40-49 years,50-59 yrears,60-69 yrears and ≥70 years groups compared to those with age ＜30 years group were 1.49 (1.22-1.80),1.88 (1.55-2.28),2.82 (2.32 3.42) and 4.60 (3.75-5.65),respectively.The HR (95％ CI) of death in patients with CD4 T cell counts ＜50 cells/μL,50-199 cells/μL,200-349 cells/μL groups compared to those of ≥350 cells/μL group were 3.28 (2.98-3.61),2.30 (2.09-2.53) and 1.39 (1.25-1.54),respectively.Male (HR-1.35,95％CI:1.28-1.42) and not switching to second line therapy (HR=4.41,95％CI:4.12-4.73) were the risk factors of death.Compared to sex transmission,blood transmission was the risk factors of death in AIDS patients.Conclusions The initiation of early HAART and timely switching to second line therapy for AIDS patients are key to prolong the survival time and to reduce AIDS related death.

Objective To analyze and investigate the survival time of dead HIV/AIDS patients after antiretroviral therapy (ART) and related factors in Henan province. Methods The database of national integrated management system of HIV/AIDS was used to collect the information of dead patients who received ART between January 2003 and December 2015. Software SPSS 23.0 was used to analyze the survival time of dead patients and related factors. Result A total of 6267 AIDS patients died after ART and the average survival time was 23.85 months (QR: 6.87-50.46 months). Within 6 months, 7-12 months and 13-24 months after ART, the numbers of dead patients were 1441 (23.00%), 652 (10.40%) and 1052 (16.79%), respectively. The number of dead cases decreased after 24 months of ART. The number of AIDS-related deaths was 5085 (81.1%);and 799 (12.7%) deaths were due to other causes, in which 179 (2.9%) were caused by accidents and 109 (1.7%) were caused by suicides. The differences in annual composition ratio of death causes during 2003-2015 had significance ( χ2=864.27, P<0.01). Twelve months, 36 months, 60 months and 120 months after ART, the survival ratios were 66.59%, 36.62%, 19.24% and 0.64% respectively. Compared with patients infected through blood donation, the HR of the patients infected through sexual transmission was 1.602 (95%CI: 1.483-1.732). Compared with patients with initial level of CD4+T lymphocyte≥350 unit/μl, the HR of patients with initial level of CD4+T lymphocyte<50 unit/μl was 2.320 (95%CI: 2.119-2.539). Compared with patients receiving second line ART, the HR of patients receiving no second line ART was 3.312 (95%CI: 3.083-3.558). Conclusion The AIDS related deaths mainly occurred in the first six months after ART. As the increase of duration of ART,the death rate decreased. Sexual transmission, low initial level of CD4+T lymphocyte and receiving no second line ART were the risk factors for the deaths of HIV/AIDS patients.