Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

Objectives:To investigate the safety and efficacy of concomitant mitral valvuloplasty(MVP)and implantation of domestic third-generation magnetically levitated Corheart 6 left ventricular assist device(LVAD). Methods:Clinical data of 13 end-stage heart failure patients who underwent Corheart 6 LVAD implantation and MVP at Central China Fuwai Hospital of Zhengzhou University from October 2021 to March 2023 were retrospectively analyzed.Mortality and complication events during hospitalization and at follow-up were collected,and changes in myocardial injury biomarkers,renal function,hemodynamics,and echocardiographic indices were observed. Results:There were no perioperative deaths and no MVP-related complications in these patients.During a mean follow-up of(14.2±5.6)months,2 patients died due to COVID-19 pneumonia and cardiac arrest respectively,11 cases(84.6%)survived.There were no recurrences of moderate-to-severe mitral regurgitation in the survived patients.Compared with preoperative value,higher cardiac output,lower central venous pressure,pulmonary artery systolic pressure(PASP),and mean pulmonary artery pressure(PAMP)were evidenced at 24 h and 72 h postoperatively,estimated glomerular filtration rate was also reduced at 1 week post operation(all P<0.010).High-sensitive troponin T level was significantly increased at 1 week post operation and then reduced at 1 month post operation,but still not returned to pre-operative level([125.5±281.9]pg/ml at baseline,[1 295.6±654.6]pg/ml at 1 week post operation and[278.0±300.5]pg/ml at 1 month post operation).Echocardiography showed that compared with preoperative period,the left ventricular ejection fraction tended to be higher at 1 and 6 months postoperatively(both P>0.017),whereas left ventricular end-diastolic dimension,PASP,and PAMP were significantly reduced(all P<0.010). Conclusions:Domestic third-generation magnetically levitated Corheart 6 LVAD implantation with concomitant MVP is safe and feasible,there is no recurrence of moderate-to-severe mitral regurgitation,a significant reduction in pulmonary artery pressure,and significant hemodynamic improvement in early to mid-term postoperatively are observed in survived patients.

Objective:To understand the clinical characteristics of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients with renal injury after antiviral therapy in Henan Province, and to explore the risk factors of renal injury.Methods:A cross-sectional study was conducted to investigate HIV infection/AIDS patients receiving antiviral therapy in Zhengzhou Sixth People′s Hospital, Anyang Fifth People′s Hospital, Hebi Third People′s Hospital, Luo Yang Zhoushan Hospital and Lankao Central Hospital in Henan Province from April 1 to September 30, 2023. The clinical information including basic data, antiviral therapy regimens and comorbidities, and laboratory test results (blood urea nitrogen, serum creatinine, blood uric acid, urine routine, urine microalbumin, urine α 1-microglobulin (α 1-MG), urine β 2-microglobulin (β 2-MG), urine retinol binding protein (RBP), urine creatinine, HIV viral load, CD4 + T lymphocyte count) were collected. Multivariate binary logistic regression was used to analyze independent risk factors for renal injury. Results:A total of 2 526 HIV infection/AIDS patients were included, with the age of (45.52±14.28) years and 2 156 (85.4%) males. The main route of transmission was sexual transmission (91.6%, 2 314/2 526). The duration of antiviral therapy was 5.00(2.92, 8.00) years. Tenofovir (TDF)+ lamivudine (3TC)+ non-nucleoside reverse transcriptase inhibitors (NNRTI) accounted for 55.3%(1 396/2 526) of the current antiviral therapy regimen. The percentage of HIV viral load <50 copies/mL was 93.0%(2 350/2 526). The CD4 + T lymphocyte count was 476(337, 645)/μL. There were 156 patients (6.2%) complicated with hepatitis B and/or hepatitis C, 205 patients (8.1%) with diabetes, 379 patients (15.0%) with hyperlipidemia, and 189 patients (7.5%) with hyperuricemia. A total of 1 040 patients (41.2%) with renal injury were found through renal function test, including 355 cases (14.1%) with estimated glomerular filtration rate (eGFR) <60 mL/(min·1.73 m 2) or urine protein positive or urine albumin creatine ratio (UACR) ≥30 mg/g, 682 patients (27.0%) with pure tubular injury presented with only positive for urinary α 1-MG, urinary β 2-MG, or urinary RBP. eGFR< 60 mL/(min·1.73 m 2) was found in 71 cases (2.8%), eGFR from 60 to 89 mL/(min·1.73 m 2) was found in 509 cases (20.2%), and eGFR≥90 mL/(min·1.73 m 2) was found in 1 946 cases (77.0%). A total of 138 patients (5.5%) were identified as having combined chronic kidney disease (CKD). Among them, 110 patients (79.7%) were in CKD stages 1 to 2, and 117 patients (84.8%) were in urinary albumin A2 grade. Multivariate analysis of 355 patients with renal injury who had eGFR<60 mL/(min·1.73 m 2) or positive urine protein in urine routine or UACR ≥30 mg/g showed that ages of 50 to 69 years old (odds ratio( OR)=2.189, 95% confidence interval ( CI) 1.333 to 3.596, P=0.002)), ≥70 years old ( OR=5.190, 95% CI 2.912 to 9.248, P<0.001), female ( OR=1.685, 95% CI 1.241 to 2.286, P=0.001), combined opportunistic infection ( OR=2.521, 95% CI 1.567 to 4.056, P<0.001), combined hepatitis B ( OR=1.962, 95% CI 1.110 to 3.467, P=0.020), combined hepatitis C ( OR=1.883, 95% CI 1.043 to 3.400, P=0.036), combined diabetes ( OR=2.703, 95% CI 1.911 to 3.821, P<0.001), using TDF for two to four years ( OR=1.674, 95% CI 1.103 to 2.459, P=0.015), using TDF for greater than or equal to five years ( OR=1.880, 95% CI 1.287 to 2.746, P=0.001), using TDF combined with lopinavir/ritonavir (LPV/r) ( OR=3.610, 95% CI 2.273 to 5.734, P<0.001) and using TDF combined with non-LPV/r ( OR=1.495, 95% CI 1.036 to 2.157, P=0.031) were the risk factors of renal injury. Conclusions:There is a high proportion of renal injury among HIV infection/AIDS patients after antiviral therapy in Henan Province, including CKD and simple renal tubular injury. Older age, female, comorbidities, and long-term use of TDF are risk factors for renal injury.

Humans ; Adult ; Serum Albumin, Human ; Consensus ; Cardiac Surgical Procedures ; Thoracic Surgery

Background: The purpose of this research was to assess the role of heparanase (HPSE)/syndecan1 (SDC1)erve growth factor (NGF) on cancer pain from melanoma. Methods: The influence of HPSE on the biological function of melanoma cells and cancer pain in a mouse model was evaluated. Immunohistochemical staining was used to analyze HPSE and SDC1. HPSE, NGF, and SDC1 were detected using western blot. Inflammatory factors were detected using ELISA assay. Results: HPSE promoted melanoma cell viability, proliferation, migration, invasion, and tumor growth, as well as cancer pain, while SST0001 treatment reversed the promoting effect of HPSE. HPSE up-regulated NGF, and NGF feedback promoted HPSE. High expression of NGF reversed the inhibitory effect of HPSE down-regulation on melanoma cell phenotype deterioration, including cell viability, proliferation, migration, and invasion. SST0001 down-regulated SDC1 expression. SDC1 reversed the inhibitory effect of SST0001 on cancer pain. Conclusions The results showed that HPSE promoted melanoma development and cancer pain by interacting with NGF/SDC1. It provides new insights to better understand the role of HPSE in melanoma and also provides a new direction for cancer pain treatment.

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

Objective:To explore the risk factors of death in patients receiving ECMO treatment and to construct a nomogram prediction model.Methods:The clinical data of 412 consecutive patients with acute heart and (or) pulmonary failure who received ECMO treatment between April 2018 and June 2022 were retrospectively included.According to the patients' in-hospital survival, univariate correlation analysis was used to select risk factor variables, and then Lasso regression was used to screen all variables, combined with common variables, combined with clinical practice, plotted a nomogram to predict the probability of early mortality, using the area under the ROC curve (AUC), Harrell C index and calibration curve were used to evaluate and internally validate the performance of the model.Decision curve analysis was applied to assess its clinical utility.Results:Cerebral infarction, diabetes, history of cardiopulmonary resuscitation, neurological complications, acute kidney injury, lactate, hemoglobin, albumin, and platelet count were risk factors for death in patients receiving ECMO ( P<0.05).At the same time, according to the actual situation and difference variables, we constructed a nomogram with high reliability to predict the probability of death. Conclusions:The study identified the risk factors of death in patients receiving ECMO, successfully constructed and validated a nomogram prediction model, and provided a simple and reliable tool for ECMO death prediction, which is of great significance for individualized treatment of patients.

The prevalence of heart failure(HF) is increasing worldwide, and mitral regurgitation(MR) is a common manifestation in patients with end-stage HF. Currently, the indications for concomitant surgical intervention of significant preoperative MR during left ventricular assist device(LVAD) implantation are still controversial. Based on discussing the etiology, classification, and pathophysiology of functional MR in patients with end-stage HF, this paper reviews the relevant factors affecting the prognosis of such patients and the progress of research related to whether to perform mitral valve surgery to intervene in significant MR during LVAD implantation, to provide a further reference for clinical practice.

Objective To investigate the efficacy of switching to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/c/F/TAF) combined with sofosbuvir/velpatasvir (SOF/VEL) in the treatment of previously untreated chronic hepatitis C patients with HIV/HCV co-infection and the changes in blood lipid levels. Methods This prospective cohort study was conducted among 10 previously untreated chronic hepatitis C patients with HIV/HCV co-infection who attended Department of Infectious Diseases in Tangdu Hospital from July 2019 to May 2021 and achieved continuous HIV suppression after antiretroviral treatment (ART). As for anti-HIV therapy, the ART regimen was switched to the E/c/F/TAF regimen for 32 weeks, and for anti-HCV therapy, the SOF/VEL regimen was started since week 4 after switching and lasted for 12 weeks. Related indices were monitored before and after switching to E/c/F/TAF for anti-HCV therapy and SOF/VEL for anti-HCV therapy, including body weight, body mass index, HCV genotype, alpha-fetoprotein, liver stiffness measurement, CD4 + T cell count, CD4 + T/CD8 + T ratio, hepatic and renal function parameters, blood lipids, HIV RNA, HCV RNA, SVR12, SVR24, and adverse reactions. The Mann-Whitney U test was used for comparison of continuous data between two groups, and a Spearman correlation analysis was performed. Results After 4 weeks of treatment with E/c/F/TAF, 10 patients (HCV genotypes 2a and 1b) had HIV RNA below the lower limit of detection (20 IU/ml) and a significant reduction in albumin ( Z =-2.801, P =0.003 7), with the other indices remaining stable, and the patients reported significant improvements in the adverse events of anti-HIV therapy with the former ART regimen. After 4 weeks of E/c/F/TAF combined with SOF/VEL, the patients had HCV RNA below the lower limit of detection (15 IU/ml), and both SVR12 and SVR24 reached 100%; after 12 weeks of anti-HCV therapy, there were significant reductions in alanine aminotransferase ( Z =-2.732, P =0.004 8) and aspartate aminotransferase ( Z =-2.501, P =0.010 7) and significant increases in total cholesterol (TC) ( Z =-2.797, P =0.003 9) and low-density lipoprotein cholesterol (LDL-C) ( Z =-2.343, P =0.018 5), with a significantly positive correlation between them ( r =0.87, P < 0.001), and all the other indices were normal. Conclusion For previously untreated chronic hepatitis C patients with HIV/HCV co-infection, switching to E/c/F/TAF combined with SOF/VEL has good efficacy, tolerability, and safety, and the combination of the two regimens can avoid drug interaction, achieve a high HCV cure rate, and maintain HIV suppression. Transient increases in TC and LDL-C are observed during combination treatment, which suggests dyslipidemia caused by HCV infection and the pharmacological action of this regimen.

Objective:To investigate the potential guiding role of fractional flow reserve(FFR) in surgical revascularization by comparing the relationship between coronary fractional flow reserve(FFR) and blood flow pattern status of bypass graft.Methods:A total of 86 patients with coronary artery disease between March 2016 to October 2019 were included in the study, with 59 males and 27 females; the age ranged from 42 to 77 years old, with an average of(58±12) years old. According to the measured FFR value of the left anterior descending artery, they were divided into severe ischemic group(FFR<0.75), boundary group(0.75≤FFR<0.80) and mild ischemic group(FFR≥0.80). Transit time flow meter(TTFM) was used to evaluate the blood flow status of the bridge vessel from the left internal thoracic artery to the left anterior descending coronary artery.Results:Mean graft flow(MGF) was measured at(21.24±5.71)ml/min, (18.25±7.72)ml/min, (16.47±7.83)ml/min in severe ischemic group, boundary group and mild ischemic group. The results of mean pulsatility index(PI) was 2.58±0.96, 3.14±1.19 and 3.53±1.34, the ratio of diastolic flow during the entire graft flow was 0.63±0.10, 0.55±0.11 and 0.53±0.11, patients appeared systolic reverse flow was 2 cases(3.6%), 3 cases(18.8%) and 3 cases (20.0%), respectively. There were statistically significant differences in MGF( P=0.027)、PI( P=0.007)、the ratio of DF( P=0.001) and the quantity of patients appeared systolic reverse flow( P=0.027) between the three groups. Conclusion:Due to increasing severity of coronary artery stenosis, MGF and the ratio of diastolic flow increased, and there appears to be an decreased PI and quantity of patients appeared systolic reverse flow. The chance of bypass graft occlusion may increase for the near and middle term in mild to moderate functional coronary artery stenosis(FFR≥0.75). For patients with severe functional coronary artery stenosis(FFR<0.75), it can obtain satisfactory flow parameters and ideal clinical outcomes.