ObjectiveTo investigate the prevalence rate of chronic non-communicable diseases （NCDs） and the association with quality of life in middle-aged and elderly patients with HIV/AIDS. MethodsThis cross-sectional study surveyed 432 patients with HIV/AIDS （aged≥45 years） in the Infectious Disease Center in Guangzhou Eighth People’s Hospital of Guangzhou Medical University， and 366 participants were included in the analysis after quality control. A questionnaire and the EuroQol 5-Dimensional 3-level version （EQ-5D-3L） were used to investigate NCDs and quality of life and Tobit regression model was used to estimate the association between chronic diseases and quality of life. ResultsAmong the 366 participants， 29（7.9%） had cardiovascular disease， 45（12.3%） had hypertension， 122（33.3%） had hyperglycemia， 151（41.3%）had hyperlipidemia，7（1.9%） had cancer， 17 （4.6%） had chronic kidney disease， 38 （10.4%） had chronic liver disease， 21（5.7%） had musculoskeletal disorders， and 253（69.1%） suffered from at least one type of chronic diseases. The median （lower and upper quartiles） of EQ-5D utility index was 1.000（0.964~1.000）. Multivariate Tobit regression results of the total population showed that cancer ［b_a=-0.08，95%CI （-0.15，-0.01），P=0.036］， chronic kidney disease ［b_a=-0.07， 95%CI （-0.12，-0.02），P=0.006］， musculoskeletal disease ［b_a=-0.09， 95%CI （-0.13， -0.05），P<0.001］， and ≥3 types of chronic diseases［b_a=-0.05， 95%CI（-0.08，-0.01），P=0.013］ were negatively correlated with EQ-5D utility index. The stratified analysis results of different CD4+T cell levels showed that hypertension ［b_a=-0.07， 95%CI （-0.12， -0.02）， P=0.007］， chronic kidney disease ［b_a=-0.10，95%CI （-0.18，-0.03）， P=0.006］， musculoskeletal disease ［b_a=-0.15， 95%CI （-0.22，-0.07）， P<0.001］ and ≥3 types of chronic diseases ［b_a=-0.09， 95%CI （-0.09， -0.01）， P<0.001］ were negatively correlated with EQ-5D utility index in the group with CD4≤500 （cells/μL）， whereas cancer［b_a=-0.11， 95%CI （-0.20，-0.01）， P=0.031］ was negatively correlated with EQ-5D utility index in the group with CD4＞500（cells/μL）. ConclusionsThe prevalence rate of chronic non-communicable diseases in middle-aged and elderly patients with HIV/AIDS is relatively high. The classification of NCDs such as cancer or chronic kidney disease or other chronic diseases and the numbers of NCDs categories are negatively correlated with quality of life. However，this association varies among patients with HIV/AIDS of different CD4+T cell levels. It is suggested that we should try to prevent and identify NCDs at an early stage， strengthen linkages and integration of health services for AIDS and chronic NCDs， and jointly manage and control AIDS with chronic diseases to improve the quality of life among people living with HIV/AIDS.

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective To explore the characteristics of blood pressure in the elderly patients with hypertensive cerebral small vessel disease(CSVD)and their correlation with traditional Chinese medicine(TCM)syndrome types.Methods A retrospective analysis was conducted in 189 elderly patients with essential hypertension.With reference to the presence or absence of CSVD,the patients were divided into CSVD group(87 cases)and non-CSVD group(102 cases).The blood pressure related parameters and clinical data obtained by four diagnostic methods of TCM in the two groups were collected,and then the characteristics of blood pressure and their correlation with TCM syndromes were analyzed with statistical methods.Results(1)CSVD group had higher values than non-CSVD group in the ambulatory blood pressure parameters of 24-hour systolic blood pressure(24hSBP),24-hour diastolic blood pressure(24hDBP),daytime systolic blood pressure(DSBP),daytime diastolic blood pressure(DDBP),nighttime systolic blood pressure(NSBP),nighttime diastolic blood pressure(NDBP),24-hour pulse pressure(24hPP),daytime pulse pressure(DPP),nighttime pulse pressure(NPP),maximum SBP,morning SBP,daytime SBP load and nighttime SBP load(P＜0.01).(2)The analysis of blood pressure variability showed that the mean value of nighttime SBP standard deviation(NSSD)in CSVD group was higher than that in the non-CSVD group(P＜0.01).(3)The analysis of circadian rhythm of blood pressure showed that there was significant difference in the comparison of circadian rhythm of ambulatory blood pressure between the two groups(P＜0.05):non-CSVD group was predominated by non-dipper type blood pressure(50 cases,49.02%)and dipper type blood pressure(31 cases,30.39%),and CSVD group was predominated by non-dipper type blood pressure(38 cases,43.68%)and super-dipper type blood pressure(31 cases,35.63%).(4)Logistic regression analysis showed that 24hSBP(OR=1.296,95%CI:1.112-1.511),maximum SBP(OR=1.074,95%CI:1.006-1.146),morning SBP(OR=1.064,95%CI:1.013-1.118),abnormal circadian rhythm of blood pressure(OR=3.736,95%CI:1.663-8.390)were the influence factors of CSVD(P＜0.05 or P＜0.01).(5)The analysis of the distribution of TCM syndrome types showed that non-CSVD group was dominated by accumulation of excess phlegm-damp syndrome(58.82%)and yin deficiency and yang hyperactivity syndrome(21.57%),and CSVD group was dominated by yin deficiency and yang hyperactivity syndrome(51.72%)and accumulation of excess phlegm-damp syndrome(21.84%).(6)The analysis of blood pressure in patients with various syndrome types showed that the DPP of patients with accumulation of excess phlegm-damp syndrome in the CSVD group was significantly higher than that in the non-CSVD group(P＜0.01),and the 24hDBP and NDBP of patients with yin deficiency and yang hyperactivity syndrome in the CSVD group were significantly higher than those in the non-CSVD group(P＜0.01).Conclusion It is indicated that 24hSBP,maximum SBP,elevated morning SBP,and abnormal blood pressure circadian rhythms may be the important risk factors for the hypertensive CSVD in the elderly.Elderly hypertensive patients with accumulation of excess phlegm-damp syndrome should pay more attention to the mean daytime pulse pressure,and elderly hypertensive patients with yin deficiency and yang hyperactivity syndrome should pay more attention to monitoring DBP.The dynamic observation and early control of the blood pressure is helpful for the prevention and treatment of CSVD in the elderly patients with hypertension.

ObjectiveTo construct and validate a clinical prediction model for diabetic kidney disease （DKD） based on optical coherence tomography angiography （OCTA）. MethodsThis study enrolled 567 diabetes patients. The random forest algorithm as well as logistic regression analysis were applied to construct the prediction model. The model discrimination and clinical usefulness were evaluated by receiver operating characteristic curve （ROC） and decision curve analysis （DCA）， respectively. ResultsThe clinical prediction model for DKD based on OCTA was constructed with area under the curve （AUC） of 0.878 and Brier score of 0.11. ConclusionsThrough multidimensional verification， the clinical prediction nomogram model based on OCTA allowed for early warning and advanced intervention of DKD.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

ObjectiveTo investigate the application of optical genome mapping （OGM） technology in detecting complex chromosomal rearrangement. MethodsWe recruited five patients who were diagnosed as complex chromosomal rearrangement at the Reproductive Medicine Center of the Sixth Affiliated Hospital of Sun Yat-sen University from January 2022 to June 2023. They underwent OGM， nanopore sequencing and pre-implantation genetic testing （PGT）. The results were compared with the results of karyotype and chromosomal microarray analysis （CMA）/ copy number variation sequencing （CNV-Seq）. ResultsOGM could detect translocation， invert inversion， and triplet translocation， which were consistent with the results of OGM and CMA/ CNV-Seq. But OGM could not detect Robertsonian translocation. ConclusionBecause of its ultra-long reads， OGM realizes the detection across repetitive regions， and it has great advantages when applied in patients with complex chromosome rearrangement or uncertain karyotype analysis. It can accurately locate breakpoints.

Aging is a crucial factor influencing postural stability control and contributing to frequent falls, yet its underlying mechanisms remain incompletely understood. This study aims to explore the effects of aging on postural stability control by comparing differences in postural stability and node strength of electroencephalogram (EEG) brain network between elderly and young people under the conditions of congruent and incongruent visual-vestibular sensory inputs. Eighteen elderly volunteers without neuromuscular disorders and eighteen young individuals participated in the present study. Virtual reality (VR) technology was employed to manipulate visual rotation stimuli (clockwise and counterclockwise), and a horizontal rotating platform was used for vestibular rotation stimuli (clockwise). Based on the directional disparity of sensory input in the horizontal plane, visual-vestibular input consistency was categorized as congruent and incongruent. Postural stability was assessed by the center of pressure (COP) trajectory, and EEG signals were collected and analyzed using directed network analysis to observe EEG brain network node connectivity strength. The results revealed that, under conditions of incongruent visual-vestibular sensory inputs, the elderly exhibited significantly inferior postural stability performance in terms of COP anterior-posterior (Y-axial) sway speed, total path length, anterior-posterior and medial-lateral sample entropy, compared to the young adults. Moreover, the node connectivity strength of visual cortex in the elderly was notably higher, while node connectivity strength of superior temporal cortex was significantly lower than that in the young adults. These findings suggest that the elderly have a heightened reliance on visual information in postural control and an impaired ability to cope with sensory conflicts arising from incongruent visual-vestibular sensory inputs, leading to compromised postural stability. The outcomes of this study hold significant implications for future assessments of balance function in the elder and fall prevention trainings.
Young Adult ; Humans ; Aged ; Adolescent ; Posture ; Postural Balance ; Aging ; Brain

OBJECTIVES: To study new biomarkers for the early diagnosis of retinopathy of prematurity (ROP) by analyzing the differences in blood metabolites based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and metabolomics. METHODS: Dried blood spots were collected from 21 infants with ROP (ROP group) and 21 infants without ROP (non-ROP group) who were hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2013 to December 2016. LC-MS/MS was used to measure the metabolites, and orthogonal partial least squares-discriminant analysis was used to search for differentially expressed metabolites and biomarkers. RESULTS: There was a significant difference in blood metabolic profiles between the ROP and non-ROP groups. The pattern recognition analysis, Score-plot, and weight analysis obtained 10 amino acids with a relatively large difference. Further statistical analysis showed that the ROP group had significant increases in blood levels of glutamic acid, leucine, aspartic acid, ornithine, and glycine compared with the non-ROP group (P<0.05). The receiver operating characteristic curve analysis showed that glutamic acid and ornithine had the highest value in diagnosing ROP. CONCLUSIONS Blood metabolites in preterm infants with ROP are different from those without ROP. Glutamic acid and ornithine are the metabolic markers for diagnosing ROP. LC-MS/MS combined with metabolomics analysis has a potential application value in the early identification and diagnosis of ROP.
Infant, Newborn ; Infant ; Humans ; Tandem Mass Spectrometry ; Infant, Premature ; Chromatography, Liquid ; Retinopathy of Prematurity/diagnosis* ; Glutamic Acid ; Ornithine