Objective:To investigate the role of the CD38/p53/ME1 axis in regulating T cell mitochondrial function and senescence during HIV infection.Methods:The expression of CD38 on T cells was examined in HIV-infected individuals receiving antiretroviral therapy(ART), untreated HIV-infected individuals, and HIV-negative healthy controls. Flow cytometry was used to compare senescence markers and mitochondrial function between CD38 + and CD38 - T cells. Malic enzyme 1(ME1) mRNA levels were measured by qRT-PCR in T cells treated with the CD38 inhibitor 78c. Mitochondrial function and senescence were assessed in T cells treated with an ME1 inhibitor. The regulatory mechanism of CD38-mediated ME1 downregulation was further explored. Results:Compared to healthy controls, T cells from HIV-infected individuals exhibited significantly elevated CD38 expression, which persisted despite ART. CD38 + T cells showed increased senescence (CD28 -CD57 + subset) and mitochondrial dysfunction[depolarization and reactive oxygen species(ROS) accumulation]. CD38 inhibition upregulated ME1 mRNA level ( P<0.05). ME1 suppression led to mitochondrial impairment (reduced membrane potential and elevated ROS) and senescence in T cells. Mechanistically, CD38 depletion increased NAD + levels and SIRT1 activity, while SIRT1/p53 inhibition rescued ME1 expression, suggesting CD38 regulates ME1 via the NAD + /SIRT1/p53 axis. Conclusions:The CD38/p53/ME1 axis drives T cell senescence in HIV infection by disrupting mitochondrial function. Targeting this pathway may ameliorate CD38-associated T cell dysfunction and immune aging.

Objective:To explore the value of contrast-enhaoced echocardiography for measuring pulmonary transit time（PTT）in assessing heart failure after percutaneous coronary intervention（PCI）in acute ST-segment elevation myocardial infarction（STEMI）patients.Methods:From September 2023 to September 2024，120 patients with STEMI undergoing PCI at Hunan Provincial People's Hospital were prospectively selected and divided into a heart failure group（ n=42）and a non-heart failure group（ n=78）according to the guidelines. The differences in general clinical data，laboratory parameters，and echocardiographic parameters between the two groups were compared. The diagnostic efficacies of PTT，normalized PTT（nPTT），and N-terminal pro-B-type natriuretic peptide（NT-proBNP）were analyzed. Consistency between them and New York Heart Association（NYHA）heart function classification was tested. Results:Compared to the non-heart failure group，the NT-proBNP，PTT，and nPTT values in the heart failure group were significantly increased（all P<0.05）. The area under the curve（AUC）of nPTT was 0.944，better than that of PTT and NT-proBNP（AUC=0.871，0.887）. After K-means clustering reclassified patients into four levels based on nPTT values，nPTT classification showed moderate consistency with NYHA classification（Kappa=0.580， P<0.001），and nPTT differed significantly across NYHA classifications（ P<0.05）. Conclusions:PTT，as an echocardiographic index for assessing cardiac function，has similar diagnostic efficacy to NT-proBNP，the nPTT is even better. It shows moderate consistency with the NYHA classification and holds potential for differentiating overlapping NYHA grades. Importantly，it offers a fresh objective way to evaluate cardiac dysfunction after PCI in STEMI patients.

Objective:To investigate the role of the CD38/p53/ME1 axis in regulating T cell mitochondrial function and senescence during HIV infection.Methods:The expression of CD38 on T cells was examined in HIV-infected individuals receiving antiretroviral therapy(ART), untreated HIV-infected individuals, and HIV-negative healthy controls. Flow cytometry was used to compare senescence markers and mitochondrial function between CD38 + and CD38 - T cells. Malic enzyme 1(ME1) mRNA levels were measured by qRT-PCR in T cells treated with the CD38 inhibitor 78c. Mitochondrial function and senescence were assessed in T cells treated with an ME1 inhibitor. The regulatory mechanism of CD38-mediated ME1 downregulation was further explored. Results:Compared to healthy controls, T cells from HIV-infected individuals exhibited significantly elevated CD38 expression, which persisted despite ART. CD38 + T cells showed increased senescence (CD28 -CD57 + subset) and mitochondrial dysfunction[depolarization and reactive oxygen species(ROS) accumulation]. CD38 inhibition upregulated ME1 mRNA level ( P<0.05). ME1 suppression led to mitochondrial impairment (reduced membrane potential and elevated ROS) and senescence in T cells. Mechanistically, CD38 depletion increased NAD + levels and SIRT1 activity, while SIRT1/p53 inhibition rescued ME1 expression, suggesting CD38 regulates ME1 via the NAD + /SIRT1/p53 axis. Conclusions:The CD38/p53/ME1 axis drives T cell senescence in HIV infection by disrupting mitochondrial function. Targeting this pathway may ameliorate CD38-associated T cell dysfunction and immune aging.

Objective:To explore the value of contrast-enhaoced echocardiography for measuring pulmonary transit time（PTT）in assessing heart failure after percutaneous coronary intervention（PCI）in acute ST-segment elevation myocardial infarction（STEMI）patients.Methods:From September 2023 to September 2024，120 patients with STEMI undergoing PCI at Hunan Provincial People's Hospital were prospectively selected and divided into a heart failure group（ n=42）and a non-heart failure group（ n=78）according to the guidelines. The differences in general clinical data，laboratory parameters，and echocardiographic parameters between the two groups were compared. The diagnostic efficacies of PTT，normalized PTT（nPTT），and N-terminal pro-B-type natriuretic peptide（NT-proBNP）were analyzed. Consistency between them and New York Heart Association（NYHA）heart function classification was tested. Results:Compared to the non-heart failure group，the NT-proBNP，PTT，and nPTT values in the heart failure group were significantly increased（all P<0.05）. The area under the curve（AUC）of nPTT was 0.944，better than that of PTT and NT-proBNP（AUC=0.871，0.887）. After K-means clustering reclassified patients into four levels based on nPTT values，nPTT classification showed moderate consistency with NYHA classification（Kappa=0.580， P<0.001），and nPTT differed significantly across NYHA classifications（ P<0.05）. Conclusions:PTT，as an echocardiographic index for assessing cardiac function，has similar diagnostic efficacy to NT-proBNP，the nPTT is even better. It shows moderate consistency with the NYHA classification and holds potential for differentiating overlapping NYHA grades. Importantly，it offers a fresh objective way to evaluate cardiac dysfunction after PCI in STEMI patients.

Objective To explore the relationship between the expression levels of serum cingulate protein(CGN)and polyligand glycan 1(SDC-1)and the disease condition and outcome of hypertensive basal ganglia hemorrhage(HBGH).Methods A total of 123 patients with HBGH admitted to the Second People's Hospi-tal of Lianyungang from February 2019 to February 2022 were selected as the study objects,and 120 healthy volunteers who underwent physical examination in the hospital during the same period were selected as the health group.Serum CGN and SDC-1 expression levels were detected in the two groups.According to the dis-ease outcome,the patients were divided into the improved group(92 cases)and the deteriorated group(31 ca-ses).Receiver operating characteristic(ROC)curve and the area under the curve(AUC)were used to analyze the predictive value of serum CGN and SDC-1 expression levels on the disease outcome of patients with HB-GH.Results Serum CGN and SDC-1 expression levels in the severe group were higher than those in the mod-erate group and the mild group,and serum CGN and SDC-1 levels in the moderate group were higher than those in the mild group,and the differences were statistically significant(P＜0.05).Serum CGN and SDC-1 expression levels in HBGH patients in three groups were higher than those in health group,and the differences were statistically significant(P＜0.05).Serum CGN and SDC-1 expression levels in the deteriorated group were higher than those in the improved group,and the differences were statistically significant(P＜0.05).The AUC of serum CGN and SDC-1 for predicting the disease outcome of HBGH patients was 0.742(95％CI:0.792-0.697)and 0.861(95％CI:0.906-0.910),respectively,and the AUC of the combination of the two was 0.917(95％CI:0.962-0.870).The amount of blood loss and ventricular rupture in the deteriorated group were higher than those in the improved group,and the Glasgow Coma Scale(GCS)score on admission was lower than that in the improved group,and the differences were statistically significant(P＜0.05).Multi-variate Logistic regression analysis showed that serum CGN≥51.63 pg/mL(OR=3.815),serum SDC-1≥450.67 μg/L(OR=4.230)and GCS score ≤8(OR=5.333)were the influencing factors for disease outcome of HBGH patients(P＜0.05).Conclusion The increased expression levels of serum CGN and SDC-1 are closely related to the disease aggravation and the deterioration of the disease outcome in patients with HBGH,and they have certain predictive value for the disease outcome in patients with HBGH.

Objective To explore the application effect of 3D printed heart models in the training of young cardiac surgeons, and evaluate their application value in surgical simulation and skill improvement. Methods Eight young cardiac surgeons were selected form West China Hospital as the trainees. Before training, the Hands-On Surgical Training-Congenital Heart Surgery (HOST-CHS) operation scores of the 8 cardiac surgeons were obtained after operating on 2 pig heart models of ventricular septal defect (VSD). Subsequently, simulation training was conducted on a 3D printed peri-membrane VSD heart model for 6 weeks, once a week. After the training, all trainees completed 2 pig heart VSD repair surgeries. The improvement of doctors’ skills was evaluated through survey questionnaires, HOST-CHS scores, and operation time after training. Results Before the training, the average HOST-CHS score of the 8 trainees was 52.2±6.3 points, and the average time for VSD repair was 54.7±7.1 min. During the 6-week simulation training using 3D printed models, the total score of HOST-CHS for the 8 trainees gradually increased (P<0.001), and the time required to complete VSD repair was shortened (P<0.001). The trainees had the most significant improvement in scores of surgical cognition and protective awareness. The survey results showed that trainees were generally very satisfied with the effectiveness of 3D model simulation training. Conclusion The 3D printed VSD model demonstrates significant application advantages in the training of young cardiac surgeons. By providing highly realistic anatomical structures, 3D models can effectively enhance surgeons’ surgical skills. It is suggested to further promote the application of 3D printing technology in medical education, providing strong support for cultivating high-quality cardiac surgeons.

Objective:To investigate the long-term death of patients with ischemic stroke and its influencing factors.Methods:Based on the data of patients with ischemic stroke in the multi-center oral fibrinogen-lowering drug secondary prevention database, the follow-up patient information and the cause of death were registered through the epidemiological investigation method, and then compared with the baseline data of patients in the original database.Results:A total of 278 patients completed the follow-up, and 166 were in lumbrokinase group and 112 were in control group. There were 124 deaths (44.6%) within 10 years, of which 92 (74.2%) were vascular deaths. In the lumbrokinase group, 74 patients (44.6%) died of all causes and 55 (33.1%) died of vascular diseases; in the control group, 50 (44.6%) died of all causes and 37 (33.0%) died of vascular diseases. Cox proportional risk model analysis showed that lumbrokinase treatment had no significant effect on the 10-year survival rate of patients with ischemic stroke. The analysis of death influencing factors showed that the baseline international normalized ratio (INR) was significantly associated with the 10-year non-vascular death risk of patients (hazard ratio [ HR] 1.98, 95% confidence interval [ CI] 1.21-3.25; P=0.006). The greater the decrease of tissue plasminogen activator (tPA) within half a year, the lower the 10-year all-cause mortality risk ( HR 0.94, 95% CI 0.90-0.99; P=0.011); the greater the decrease in INR within one year , the lower the 10-year vascular death risk ( HR 0.41, 95% CI 0.17-0.96; P=0.040); the greater the decrease of D-dimer within one year , the higher the risk of the 10-year vascular death ( HR 1.37, 95% CI 1.02-1.83; P=0.034). The greater the decrease of INR in patients with ischemic stroke within one year, the higher the 10-year non-vascular death risk ( HR 2.15, 95% CI 1.29-3.59; P=0.004). Conclusions:The 10-year mortality rate of patients with ischemic stroke is higher, and about 3/4 are vascular deaths. The fibrinogen-lowering treatment in the acute stage has no significant effect on the 10-year all-cause mortality of patients with ischemic stroke. The greater the decrease of tPA in half a year, the lower the all-cause mortality; the greater the decrease of D-dimer level at baseline and within 1 year, the higher the 10-year vascular death; the greater the decrease of INR at baseline and within 1 year, the higher the 10-year non-vascular death risk.

Objective:To investigate the number of necroptotic renal tubular epithelial cells in renal tissues of patients with chronic kidney disease (CKD) and the correlation with clinicopathologic parameters, and explore its role in the progression of the excessive loss of renal tubular cells and chronic kidney injury.Methods:Renal tissue samples from 60 patients (18-65 years old) with CKD proven by kidney biopsy in the First Affiliated Hospital of Hainan Medical University from June 2017 to June 2019 were collected. According to internationally accepted K/DOQI guidelines, the patients were divided into 1-4 stages of CKD, with 15 cases in each stage. The number of necroptotic renal tubular epithelial cells in patients with different stages of CKD was detected using receptor-interacting protein 3 (RIP3) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) fluorescent staining, and the expression of RIP3 and MLKL, marker protein of necroptosis, was detected by immunohistochemistry. Pearson correlation analysis was used to analyze the correlation between the percentage of necroptotic renal tubular epithelial cells and clinicopathologic parameters. In addition, the expression of angiotensinogen Ⅱ receptor (AT2R) in renal tissue and its correlation with the percentage of necroptotic renal tubular epithelial cells were analyzed.Results:With the development of CKD, the structural destruction of renal tubules in patients with CKD was gradually aggravated, and the renal tubules in the corresponding areas were atrophied, accompanied by worsening interstitial fibrosis. The adjacent renal tubules were focally dilated and numerous protein tubules were seen in the tubules. Importantly, renal tubular injury score in second and third stage of CKD was significantly higher than that in control group (both P<0.01). TUNEL+RIP3 immunofluorescence staining results showed that the percentage of TUNEL/RIP3 double positive renal tubular epithelial cells (necroptotic renal tubular epithelial cells) in renal tubules of the second and third stage of CKD was higher (all P<0.01). Immunohistochemical results showed that RIP3, MLKL and AT2R proteins were mainly expressed in cytoplasm of renal tubular epithelial cells, and the expression of RIP3, MLKL and AT2R in renal tubular epithelial cells was higher in the second and third stage of CKD patients (all P<0.05). Pearson correlation analysis showed that the percentage of necroptotic renal tubular epithelial cells was positively correlated with blood urea nitrogen ( r=0.514, P=0.003), serum creatinine ( r=0.507, P=0.019), serum cystatin C ( r=0.571, P=0.026), serum uric acid ( r=0.592, P=0.008), renal tubules injury score ( r=0.901, P<0.001), renal interstitial fibrosis index ( r=0.700, P=0.001) and the expression of AT2R protein in renal tissue ( r=0.715, P=0.001). Conclusions:As CKD progresses, necroptosis of renal tubular epithelial cells in CKD patients occurs. The necroptotic cell death may be an important factor leading to renal tubular epithelial cell excessive death and the progression of chronic kidney injury. Furthermore, necroptosis of renal tubular epithelial cells may be related to the high expression of AT2R in kidney tissue.

Hyaluronic acid (HA) is a natural ligand of tumor-targeted drug delivery systems (DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors (HARE and LYVE-1) are also overexpressing in the reticuloendothelial system (RES). Therefore, polyethylene glycol (PEG) modification of HA-based DDS is necessary to reduce RES capture. Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement, significantly compromising the antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform (Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage. The and investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and nonspecific biodistribution.

Objective: To evaluate clinical efficacy and safety of microneedle-mediated intradermal injection with hyaluronic acid for the treatment of sensitive skin. Methods: A total of 53 female patients aged 21-54 years and diagnosed with sensitive skin were enrolled from Department of Cosmetic Dermatology, Dermatology Hospital of Southern Medical University from January to June in 2018, and were divided into 3 groups by using a random number generator and a residue-based method: high-pressure jet injection group (n = 23) receiving high-pressure jet injection with hyaluronic acid on the right side of the face (treatment side) and high-pressure jet injection with 0.9% sodium chloride solution on the left side of the face (control side) once every 2 weeks, microneedle injection group (n = 15) receiving microneedle-mediated injection with hyaluronic acid on the right side of the face (treatment side) and microneedle-mediated injection with 0.9% sodium chloride solution on the left side of the face (control side) once every 4 weeks, combination group (n = 15) receiving microneedle-mediated injection with hyaluronic acid on the right side of the face (treatment side) and high-pressure jet injection with hyaluronic acid on the left side of the face (control side) once every 4 weeks. All the patients in the above 3 groups received 4 consecutive sessions of treatment. Before the initial treatment and 2 weeks after the final treatment, erythema and skin pore scores were determined on the right and left sides of the face by using VISIA facial imaging system, lactic acid stinging test was performed, and skin sensitivity including severity of itching, dryness, erythema and scaling was evaluated. Two weeks after the final treatment, the overall improvement was evaluated with the Global Aesthetic Improvement Scale (GAIS) by clinicians and patients. Adverse reactions were recorded during and after treatment. Statistical analysis was carried out by using paired t test, Wilcoxon sign rank sum test and chi-square test. Results: Two weeks after the final treatment, the improvement of skin pore score in the treatment side was superior to that in the control side in the high-pressure jet injection group (t = 2.19, P = 0.03) , while no significant difference in the improvement of erythema score was observed between the treatment side and control side (t = 1.10, P = 0.27) ; in the microneedle injection group, the improvement of erythema and skin pore scores was greater in the treatment side than in the control side (t = 2.47, 3.02, both P = 0.01) ; in the combination group, the VISIA erythema score in the treatment and control sides was 0.59 ± 0.25 and 0.85 ± 0.31 respectively, the improvement of erythema score in the treatment side was superior to that in the control side (t = 5.02, P < 0.01) , while there was no significant difference in the improvement of skin pore score between the treatment side and control side (P > 0.05) . Two weeks after the final treatment, the severity of itching, dryness and scaling was significantly improved in both the treatment and control sides in the 3 groups compared with those before the initial treatment (P < 0.05) , while the severity of erythema was significantly improved only in the treatment side in the microneedle injection group and combination group when compared with that before the initial treatment (Z = -2.236, -2.887, respectively, both P < 0.05) . Moreover, both the microneedle injection group and combination group showed significantly decreased severity of erythema in the treatment side compared with that in the control side two weeks after the final treatment (Z = -2.646, -2.887, respectively, both P < 0.05) . Two weeks after the final treatment, the positive rate of the lactic acid stinging test significantly decreased in the treatment side compared with that before the initial treatment in the microneedle injection group (χ² = 4.821, P = 0.028) , but showed no significant changes in the other groups (all P > 0.05) . No severe adverse reactions were observed during or after the treatment. Conclusion Microneedle intradermal injection with hyaluronic acid can effectively and safely improve erythema, skin pore and sensitive symptoms in patients with sensitive skin.