Objective Our study aimed to provide a comprehensive overview of the current status and dynamic trends of the human immunodeficiency virus (HIV) prevalence in Sichuan,the second most heavily affected province in China,and to explore future interventions. Methods The epidemiological,behavioral,and population census data from multiple sources were analyzed to extract inputs for an acquired immunodeficiency syndrome (AIDS) epidemic model (AEM). Baseline curves,derived from historical trends in HIV prevalence,were used,and the AEM was employed to examine future intervention scenarios. Results In 2015,the modeled data suggested an adult HIV prevalence of 0.191％ in Sichuan,with an estimated 128,766 people living with HIV/AIDS and 16,983 individuals with newly diagnosed infections. Considering current high-risk behaviors,the model predicts an increase in the adult prevalence to 0.306％ by 2025,projecting an estimated 212,168 people living with HIV/AIDS and 16,555 individuals with newly diagnosed infections. Conclusion Heterosexual transmission will likely emerge as the primary mode of AIDS transmission in Sichuan. Furthermore,we anticipate a stabilization in the incidence of AIDS with a concurrent increase in prevalence. Implementing comprehensive intervention measures aimed at high-risk groups could effectively alleviate the spread of AIDS in Sichuan.

Objective:To explore the relationship between drug resistance occurrence and the distribution pattern of polymorphic loci in individuals with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) treated with highly active anti-retroviral therapy (HAART).Methods:HAART-failed HIV/AIDS patients who successfully amplified the gene sequences of the pol region between June 2015 and December 2021 from 16 prefecture-level administrative regions in Yunnan Province were included.The resistant sequences were classified using the human immunodeficiency virus (HIV) basic local alignment search tool (BLAST) and validated through MEGA 6.0, and the obtained sequences were submitted to the Stanford University HIV Drug Resistance Database to identify drug resistance loci. The distribution of polymorphic loci was analyzed across patients exhibiting varying degrees of drug resistance, different treatment regimens and distinct HIV-1 subtypes.Changes of the frequencies of polymorphic loci in patients with different degrees of drug resistance were analyzed using trend chi-square test. Statistical comparisons and further paired comparisons were performed using chi-square test.Results:Gene sequences were amplified from 1 453 patients, and the resistance testing results showed 954 sensitive, 224 potentially or low resistant, 189 moderately resistant, and 86 highly resistant patients. The frequencies of mutations I15V, L19I, D60E in the HIV-1 protease region (PR region) and E36A, T39D, S48T mutations in the HIV-1 reverse transcriptase region (RT region) showed a decreasing trend as the degree of HIV-1 resistance escalated ( χ2trend=19.86, 9.16, 13.66, 37.64, 18.44 and 40.86, respectively, all P<0.01). Conversely, the mutations V77I in the PR region and K122E in the RT region showed an ascending trend ( χ2trend=12.19 and 10.03, respectively, both P<0.01). Distinct treatment groups, namely zidovudine (AZT)+ lamivudine (3TC)+ lopinavir/ritonavir (LPV/r), AZT+ 3TC+ efavirenz (EFV), AZT+ 3TC+ nevirapine (NVP), and tenofovir (TDF)+ 3TC+ EFV, were examined. Statistically significant differences in the frequencies of mutations E35D, M36I, and D60E in the PR region, as well as S48T, K122E, and R211K in the RT region, were observed among these treatment groups ( χ2=22.46, 9.32, 14.46, 26.85, 18.92 and 24.26, respectively, all P<0.05). In paired comparisons, AZT+ 3TC+ LPV/r group displayed higher frequencies of E35D, M36I, and D60E mutations, the AZT+ 3TC+ EFV group showed a higher frequency of S48T mutation, the AZT+ 3TC+ NVP group showed a higher frequency of K122E mutation, and the TDF+ 3TC+ EFV group exhibited a higher frequency of R211K mutation, all with statistically significant differences (all P<0.008). The differences in the frequencies of T12S, I15V, L19I, M36I, V77I, L89M in the PR region and E53D, I135V, S162C, R211K, K277R in the RT region among circulating recombinant form (CRF)08_BC, CRF07_BC and CRF01_AE subtype group were statistically significant ( χ2=693.60, 712.51, 798.11, 434.85, 386.91, 657.78, 932.58, 409.21, 344.39, 469.44 and 260.48, respectively, all P<0.001). In paired comparisons, the frequencies of T12S, I15V, L19I, E53D, I135V, S162C and R211K in CRF08_BC subtype, the frequencies of V77I and K277R in CRF07_BC subtype, and the frequencies of M36I and L89M in CRF01_AE subtype were higher than those in the other two groups, and the differences were all statistically significant (all P<0.017). Conclusions:The polymorphic loci resulting from HIV-1 HAART failure show different distribution patterns across various degrees of drug resistance, treatment regimens and HIV-1 subtypes.These loci demonstrate both specific and shared characteristics. It is necessary to enhance the surveillance of select polymorphic loci.

Objective:To evaluate the safety and efficacy at 1-year follow-up of the use of drug-coated balloon (DCB) for the treatment of femoropopliteal in-stent restenosis (ISR).Methods:This study enrolled 252 patients undergoing Orchid DCB angioplasty for peripheral arterial disease in the femoral-popliteal segment. The clinical data were retrospectively analyzed.Results:Forty-nine patients were eligible, including 29 (59.2%) chronic total occlusions belonging to TransAtlantic Inter-Society Consensus-Ⅱ(TASC Ⅱ) D, 7 (14.3%) thrombosis, and 14 (28.6%) moderate to severe calcifications. The mean lesion length was (215.9±97.1) mm. 69.4% were of occlusive lesions (Tosaka Ⅲ category). Only 1 provisional stent was implanted. 98% patients had severe claudication or even worse. Of these cases, 34 (73.9%) showed improvements in Rutherford category, while 11 (23.9%) did not change and 1 (2.2%) case deteriorated. The average value of ABI was 0.478±0.264 before surgery and 0.907±0.207 at the end of follow-up. The improvement in Rutherford category ( P<0.01) and ABI ( P<0.005) were both significant. The primary patency (PP) was 80.4%, and the freedom from clinically driven TLR was 84.8% at 1 year. During the follow-up period, there was no all-cause death and major limb amputation. Conclusion:This multicenter study demonstrated the effectiveness of DCB as a treatment for complicated and extensive ISR lesions within 12 months.

Objective: To learn the genotypic drug resistance of men who have sex with men ( MSM ) with HIV who failed in antiviral therapy in Yunnan Province, in order to provide basis for improving the effect of antiviral therapy. Methods: The patients who were infected with HIV-1, homosexual transmitted and failed in antiviral therapy in Yunnan Province from 2014 to 2019 were recruited. Their plasma samples were tested by reverse transcription nested polymerase chain reaction ( RT-nPCR ) , the fragments were spliced using ContigExpress, and the resistance to 8 protease inhibitors ( PIs ) , 7 nucleoside reverse transcriptase inhibitors ( NRTIs ) and 5 non-nucleoside reverse transcriptase inhibitors ( NNRTIs ) were obtained from the HIV drug resistance data website of Stanford University. Results: A total of 205 HIV/AIDS cases were included, 169 positive plasma samples were amplified, 112 cases were drug resistant, and the rate of drug resistance was 66.27%. The patients who were aged 30-49 years ( 76.09% ) , had genotype of CRF01_AE ( 76.34% ) or treated by AZT+3TC+NVP ( 77.08% ) had higher resistance rate. The resistance rates of NNRTIs, NRTIs and PIs were 62.72%, 49.70% and 2.96%, respectively; the resistance rates of NVP and EFV in NNRTIs were 62.72% and 61.54%. The main mutation site associated with NNRTIs was K103, accounting for 21.89% ( 37 cases ) ; the main mutation site associated with NRTIs was M184, accounting for 39.64% ( 67 cases ) ; the main mutation sites associated with PIs were M46L/K, accounting for 2.96% ( 5 cases ) , resulting in high resistance to NFV. Conclusions The drug resistance rate of HIV-infected MSM with failure of antiviral therapy in Yunnan Province is relatively high, with CRF01_AE as the main gene subtype of drug resistance. The drug resistance rate of NNRTIs is relatively high, especially NVP and EFV.

Objective: To establish a method for in vitro expansion of regulatory T cells (Tregs) for clinical study and immunotherapy. Methods: CD4⁺ T cells were isolated from BALB/c spleens by magnetic activated cell sorting (MACS), then cultured in 24-well plates coated with anti-CD3/CD28 microbeads in the presence of 100 U/ml interleukin-2 (IL-2) and 5 ng/ml recombinant human transforming growth factor-β (rhTGF-β). The purity of the expanded Tregs were tested by flow cytometry. In vitro inhibition of CD4⁺ CD25^-T cells response by expanded Tregs was measured by mixed lymphocyte reaction test. The number and the viability of the expanded Tregs were detemined by trypan blue staining. Results: Tregs were expanded up to 20 folds after 5 days in culture, and the activity was (93±4)%. The purity of expanded Tregs were (79.1±1.5)%, and maintained suppressive ability. Conclusions We can obtain large numbers of Tregs with highly purity and suppressive ability, thereby providing a solution to the availability of sufficient Tregs in clinical study and immunotherapy.

Objective To analyze the genetic structure and recombination characteristics of a new-ly discovered HIV-1 unique recombinant strain in Yunnan Province. Methods During a test for drug-resist-ant HIV genotypes in Yunnan Province in 2016, a recombinant fragment was found in the pol region of a HIV-1 strain isolated from a patient. Two overlapping segments of the HIV-1 genome were amplified by RT-PCR, and then the products were sequenced. Recombination analysis was performed using RIP, jpHMM and SimPlot3. 5 software. A phylogenetic tree was constructed for homology analysis by Neighbor-joining method using MEGA6. 06 software. Results A nearly full-length HIV-1 gene sequence with 8590 bp in length was obtained. Breakpoint analysis indicated that the sequence consisted of CRF01_AE and fragments of B and C subtypes. CRF01_AE was used as the backbone with B and C subtype fragments inserted. The positions were 791 to 1171 for CRF01_AE, 1172 to 2652 for C subtype fragment, 2653 to 2977 for B subtype frag-ment, and 2978 to 9380 for CRF01_AE using HIV-1 HXB2 as the reference strain. Conclusions Some new strains formed by cross-recombination of CRF01_AE and B and C subtypes were discovered in Yunnan Province in recent years. It was found that the recombination pattern of the newly discovered strain was com-plex, suggesting that close attention should be paid to the changes in epidemic trends, which was of great im-portance to understand the current prevalence and epidemic trends of HIV-1.

Objective To investigate the influence factors of mortality among human immunodeficiency virus (HIV)-infected children under highly active antiretroviral therapy (HAART).Methods Retrospective cohort study of 652 children initiated HAART from 2005 to 2014 was conducted,and enrolled patients were followed-up until December,2015.Survival data was analyzed using Kaplan-Meier method and Cox regression model was used to identify independent predictors of mortality among these children on HARRT.Chi-square test and Fisher's exact test were used for comparison between groups.Results Overall,26 of the children died over a follow-up period of 3 116.24 child-years,with a mortality rate of 0.83 per 100 child-years.Twelve (46％)of deaths occurred during the first six months after starting HAART.Cox regression analysis of variables showed that the World Health Organization (WHO) clinical stages Ⅲ/Ⅳ (hazard rate [HR] =10.717,95％confidence interal [95％ CI]:4.189-4.749,P =0.000),baseline hemoglobin ＜ 80 g/L (HR =14.768,95 ％ CI:5.721-38.125,P =0.000),tuberculosis co-infection (HR =4.794,95％ CI:2.105-10.918,P =0.000),baseline CD4+T lymphocyte ＜ 50 cells/μL (HR =4.219,95％ CI:1.524-11.680,P =0.006),weight-for-age z-score ＜-2 (HR =2.983,95 ％ CI:1.094-8.135,P =0.033) were independently associated with death,whereas the age ＜ 7 year-old at HAART initiation was protectire (HR =0.293,95％ CI:0.126-0.684,P =0.005).Conclusions The mortality of children receiving HAART is strongly associated with WHO stages Ⅲ/Ⅳ,hemoglobin ＜ 80 g/L,weight-for-age z-score ＜-2,tuberculosis co-infection and older age at treatment.

Objective To investigate the effect of catheter-based peripheral sympathetic denervation (CPSD) on peripheral artery sympathetic tone of New Zealand rabbits.Methods Twenty New Zealand rabbits were randomly divided into CPSD group and control group (each n =10).Endovascular radiofrequency ablation above the bifurcation of the abdominal aorta was performed on the rabbits in CPSD group.Norepinephrine was infused with continuous trans-arterial pumping in both two groups.And laser Doppler flowmetry was used to measure the peripheral microperfusion and temperature of right hindlimb of rabbits.The changes of the peripheral microperfusion and temperature before (resting state) and after norepinephrine infused (norepinephrine load state) were compared between the two groups.Results Eight rabbits completed the procedure in each group.The change of peripheral microperfusion between resting and norepinephrine load states in CSPD group was lower than that in control group ([-37.19±22.56]％ vs [-57.02％±10.12]％,P=0.04),whereas the change of temperature was not significantly different between the two groups ([0.35±0.50]℃ vs [-0.21± 1.83]℃,P=0.43),while significant difference was noticed when two rabbits with abnormal temperature change in control group were neglected ([0.34± 0.50] ℃ vs [-1.14 ±0.72] ℃,P＜0.01).Conclusion CPSD can be used to decrease the peripheral artery sympathetic tone of New Zealand rabbits,and may play an important role in relieving symptoms of critical limb ischemia.

Objective To observe the clinical value of cone-beam computed tomography (CBCT) combined with iGuide system in percutaneous transthoracic needle biopsy (PTNB) of pulmonary lesions.Methods A total of 30 patients with solitary lung lesion underwent PTNB procedures were enrolled.The needle path was planned with iGuide system and 3D CT-like MPR images after CBCT.A coaxial system with 18-gauge cutting needle was used for biopsy.Procedure related data,complications and radiation exposure of patients were recorded.Results Among 30 patients,malignant lesions were found in 24,and benign lesions were in 6 patients.On PTNB,28 patients were correctly diagnosed,1 case was with insufficient samples but obtained correct pathologic result with second biopsy,1 case was false-negative finding.The diagnostic accuracy,sensitivity,specificity,positive predictive value and negative predictive value of PTNB in diagnosis of lung diseases was 96.67％ (29/30),96.00％ (24/25),100％ (5/5),100％ (24/24) and 83.33％ (5/6),respectively.The mean procedure time was (13.03+3.61)min,and exposure dose was (7.95+4.57)mSv.After PTNB procedures,pneumothorax and hemoptysis occurred in 6 (6/30,20.00％) and 3 (3/30,10.00％) patients,respectively.Conclusion CBCT combined with iGuide system for guiding PTNB is accurate and safe with reasonable radiation exposure.

Objective To investigate the effectiveness of endovascular technique in treatment of acute arterial hemorrhage of abdominal organs.Methods Totally 159 cases (145 patients) acute arterial hemorrhage of abdominal organs were enrolled.All patients underwent emergency transarterial angiography.Endovascular treatment by spring coil,gelatin sponge,or covered stent were in 40 cases.The success rate of immediate and long-term hemostasis was judged by the postoperative radiography,symptoms and the changes of vital signs and laboratory results.Results The positive signs in angiography were observed in 47 among the total 159 cases (47/159,29.56％).Seventy-seven postoperative hemorrhage cases underwent angiography and 29 cases (29/77,37.66 ％) were positive,82 non-operative hemorrhage cases underwent angiography and 18 cases (18/82,21.95％) were positive.The difference was statistical significant (P＜0.05).Endovascular treat ment were performed in 40 cases (33 by spring coils,4 by gelatin sponge and 3 by covered stent).Hemorrhages were con trolled immediately in all the 40 cases after embolization and the success rate were 100％.Conclusion Endovascular tech nique is minimal invasive,and it is an effective method for treatment of acute arterial hemorrhage in abdominal organs.