NLRP3 inflammasome-mediated premature immunosenescence drives diabetic vascular aging dependent on the induction of perivascular adipose tissue dysfunction.

AIMS: The vascular aging process accelerated by type 2 diabetes mellitus (T2DM) is responsible for the elevated risk of associated cardiovascular diseases (CVDs). Metabolic disorder-induced immune senescence has been implicated in multi-organ/tissue damage. Herein, we sought to determine the role of immunosenescence in diabetic vascular aging and to investigate the underlying mechanisms. METHODS AND RESULTS: Aging hallmarks of the immune system appear prior to the vasculature in streptozotocin (STZ)/high-fat diet (HFD)-induced T2DM mice or db/db mice. Transplantation of aged splenocytes or diabetic splenocytes into young mice triggered vascular senescence and injury compared to normal control splenocyte transfer. RNA-seq profile and validation in immune tissues revealed that the Toll-like receptor 4 (TLR4)- Nuclear factor-kappa B (NF-κB) -NLRP3 axis might be the mediator of diabetic premature immunosenescence. The absence of Nlrp3 attenuated immune senescence and vascular aging during T2DM. Importantly, senescent immune cells, particularly T cells, provoked perivascular adipose tissue (PVAT) dysfunction and alternations in its secretome, which in turn impair vascular biology. In addition, senescent immune cells may uniquely affect vasoconstriction via influencing PVAT. Lastly, rapamycin alleviated diabetic immune senescence and vascular aging, which may be partly due to NLRP3 signaling inhibition. CONCLUSION: These results indicated that NLRP3 inflammasome-mediated immunosenescence precedes and drives diabetic vascular aging. The contribution of senescent immune cells to vascular aging is a combined effect of their direct effects and induction of PVAT dysfunction, the latter of which can uniquely affect vasoconstriction. We further demonstrated that infiltration of senescent T cells in PVAT was increased and associated with PVAT secretome alterations. Our findings suggest that blocking the NLRP3 pathway may prevent early immunosenescence and thus mitigate diabetic vascular aging and damage, and targeting senescent T cells or PVAT might also be the potential therapeutic approach.

Application of digitization and visualization-based muscle strength measurement in ischemic stroke patients with motor dysfunction.

Ischemic stroke stands as a prevalent neurological ailment, where a paucity of methodologies exists for the assessment of functional outcomes post-stroke. Our objective was the development of a WeChat applet for the evaluation of muscle strength and the subsequent evaluation of its validity in ischemic stroke patients experiencing motor dysfunction. The assessment encompassed Lovett and NIHSS, followed by muscle strength values (MSV) and muscle strength ratios (MSR). These metrics were then scrutinized in relation to NIHSS and Lovett, followed by examination of their interrelationships. We enrolled a cohort of 157 patients, with an average age of 65 years, consisting of 96 males and 61 females. Lovett scores in the range of 2-4 and NIHSS scores spanning from 0 to 3 were found to correspond to specific values of MSV and MSR, respectively. Upon conducting correlation analysis, we noted that both MSV and MSR exhibited significant positive correlations with Lovett scores and NIHSS. Remarkably, the correlation of MSR with Lovett scores or NIHSS surpassed that of MSV. The WeChat applet offers a means of digitization and visualization of muscle strength. It correlates well with Lovett score and NIHSS, especially MSR. This bears potential significance in guiding the rehabilitation of stroke patients.

Risk factors for post-stroke depression in patients with mild and moderate strokes.

To determine the possible risk factors for post-stroke depression in patients with mild and moderate acute strokes. A cross-sectional descriptive study was conducted involving 129 patients with mild and moderate acute strokes. The patients were divided into post-stroke depression and non-depressed stroke groups according to the Hamilton Depression Rating Scale for Depression-17 item and Patient Health Questionnaire-9 item assessments. All participants were evaluated based on clinical characteristics and a battery of scales. Patients with post-stroke depression had an increased stroke frequency, severe stroke symptoms and poor performance in activities of daily living (ADL), cognitive function, sleep quality, interest in pleasurable activities, negative life events, and utilization of social support compared to stroke patients without depression. The Negative Life Event Scale (LES) score was significantly and independently associated with an increased probability of depression in stroke patients. Negative life events were shown to be independently associated with the incidence of depression in patients with mild and moderate acute strokes, likely mediating the influence of other predictors of depression, such as a history of stroke, decreased ADL ability, and utilization of support.

Biomarkers of aging.

Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need. Here, we summarize our current knowledge of biomarkers developed for cellular, organ, and organismal levels of aging, comprising six pillars: physiological characteristics, medical imaging, histological features, cellular alterations, molecular changes, and secretory factors. To fulfill all these requisites, we propose that aging biomarkers should qualify for being specific, systemic, and clinically relevant.

Digital pathology and artificial intelligence as the next chapter in diagnostic hematopathology.

Digital pathology has a crucial role in diagnostic pathology and is increasingly a technological requirement in the field. Integration of digital slides into the pathology workflow, advanced algorithms, and computer-aided diagnostic techniques extend the frontiers of the pathologist's view beyond the microscopic slide and enable true integration of knowledge and expertise. There is clear potential for artificial intelligence (AI) breakthroughs in pathology and hematopathology. In this review article, we discuss the approach of using machine learning in the diagnosis, classification, and treatment guidelines of hematolymphoid disease, as well as recent progress of artificial intelligence in flow cytometric analysis of hematolymphoid diseases. We review these topics specifically through the potential clinical applications of CellaVision, an automated digital image analyzer of peripheral blood, and Morphogo, a novel artificial intelligence-based bone marrow analyzing system. Adoption of these new technologies will allow pathologists to streamline workflow and achieve faster turnaround time in diagnosing hematological disease.

[Effects of different low-dose of insulin glargine on antioxidation of organs in burned rats with delayed resuscitation].

OBJECTIVE: To study the antioxidant protective effects of different low-dose of insulin glargine on organs of burned rats with delayed resuscitation. METHODS: Forty male Sprague-Dawley (SD) rats were randomly divided into sham group, delayed resuscitation control group, and insulin glargine 0.5, 1.0, and 2.0 U groups, with 8 rats in each group. The rats were immersed in hot water (95.0±0.5) centigrade for 15 s to establish the third-degree scald model with 30% total body surface area. The rats in the sham group were immersed in a 37 centigrade water bath for 15 s. Insulin glargine (0.5, 1.0, 2.0 U×kg-1×d-1) was injected subcutaneously in corresponding insulin glargine group 2 hours after injury, and the same amount of normal saline was injected intraperitoneally in the delayed resuscitation control group. Intraperitoneal injection of normal saline 40 mL/kg simulated delayed resuscitation 6 hours after injury in all groups. Abdominal aortic blood samples, heart and kidney tissue were collected immediately after simulating burn in the sham group, and 24 hours after burn in other four groups. The blood glucose, myocardial enzymes [lactate dehydrogenase (LDH), creatine kinase (CK), α-hydroxybutyrate dehydrogenase (α-HBDH), and aspartate aminotransferase (AST)] and renal function indexes [blood urea nitrogen (BUN) and serum creatinine (SCr)] were measured by spectrophotometry, and the isoenzyme MB of creatine kinase (CK-MB) level was determined by immunosuppression method to evaluate the effects of different low-dose insulin glargine intervention on blood glucose, cardiac and renal functions in scalded rats with delayed resuscitation. The oxidative and antioxidant indices [xanthine oxidase (XOD), myeloperoxidase (MPO), copper-zinc superoxide dismutase (CuZn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC)] from the heart and kidney tissues of rats were detected by spectrophotometry to analyze the antioxidant effects of different low-dose insulin glargine interventions. RESULTS: Compared with the sham group, the blood glucose of the rats in the delayed resuscitation control group was significantly increased, the heart and kidney functions were significantly reduced, the oxidation capacity was enhanced, and the antioxidant indicators were significantly reduced. After the intervention of insulin glargine, with the increase of insulin glargine dose, the blood glucose, myocardial enzyme and renal function indicators of rats showed a gradual downward trend, the oxidation indicators continued to decrease, and the antioxidant indicators showed a gradual upward trend. When the dose was 2.0 U×kg-1×d-1, the blood glucose, LDH, CK, CK-MB, α-HBDH, AST, BUN, SCr, XOD and MPO were significantly lower than those in the delayed resuscitation control group [blood glucose (mmol/L): 5.91±0.25 vs. 11.76±0.36, LDH (U/L): 3 332.12±51.61 vs. 5 008.94±490.12, CK (kU/L): 0.49±0.03 vs. 0.85±0.04, CK-MB (U/L): 125.40±12.19 vs. 267.52±11.63, α-HBDH (U/L): 122.99±5.37 vs. 240.85±13.99, AST (U/L): 11.95±1.81 vs. 17.87±1.57, BUN (mmol/L): 4.72±0.15 vs. 7.16±0.34, SCr (µmol/L): 87.11±6.51 vs. 137.50±11.36, XOD (U/g): 166.29±3.27 vs. 204.90±4.82 in heart tissue, 63.51±1.46 vs. 79.69±1.75 in kidney tissue, MPO (U/g): 1.05±0.02 vs. 1.55±0.06 in heart tissue, 1.04±0.04 vs. 1.87±0.01 in kidney tissue, all P < 0.05], and CuZn-SOD, CAT, GSH-Px and T-AOC were significantly higher than those in the delayed resuscitation control group [CuZn-SOD (kU/g): 82.95±2.69 vs. 56.52±2.26 in heart tissue, 94.50±2.73 vs. 62.02±1.66 in kidney tissue, CAT (U/g): 36.07±2.01 vs. 15.15±2.22 in heart tissue, 184.49±4.53 vs. 156.02±3.96 in kidney tissue, GSH-Px (kU/g): 231.93±8.03 vs. 179.48±3.15 in heart tissue, 239.63±7.30 vs. 172.20±2.09 in kidney tissue, T-AOC (kU/g): 4.85±0.23 vs. 2.71±0.11 in heart tissue, 5.51±0.08 vs. 3.50±0.07 in kidney tissue, all P < 0.05]. CONCLUSIONS: Different low-dose of insulin glargine (≤ 2.0 U×kg-1×d-1) could exert antioxidant protection on the heart and kidney of rats with delayed resuscitation after burns, with a dose-dependent manner.

Recent Advances in Medical Image Processing.

BACKGROUND: Application and development of the artificial intelligence technology have generated a profound impact in the field of medical imaging. It helps medical personnel to make an early and more accurate diagnosis. Recently, the deep convolution neural network is emerging as a principal machine learning method in computer vision and has received significant attention in medical imaging. Key Message: In this paper, we will review recent advances in artificial intelligence, machine learning, and deep convolution neural network, focusing on their applications in medical image processing. To illustrate with a concrete example, we discuss in detail the architecture of a convolution neural network through visualization to help understand its internal working mechanism. SUMMARY: This review discusses several open questions, current trends, and critical challenges faced by medical image processing and artificial intelligence technology.

[AIDS-related knowledge, attitudes and behaviors: a prevalence survey among 309 homosexual men in a Chinese city].

OBJECTIVE: To gain an insight into the demographic characteristics and AIDS-related knowledge, attitudes and behaviors of men who have sex with men (MSM) in a Chinese city, and to offer a base for preventive measures against AIDS. METHODS: We carried out a prevalence survey, using "snowball" methods to set up survey sites in the "comrade" community, the "comrades" looking for the respondents by various means. RESULTS: Among 309 respondents, 265 (85.8%) were younger than 30 years, 187 (60.5%) received college education or above, 187 (60.5%) were government officials or employees, and 91 (29.4%) were students; 299 (96.8%) were willing or very willing to get knowledge about HIV prevention and treatment, 201 (65.1%) considered themselves as MSM, 76 (24.6%) admitted bisexuality, 117 (37.9%) had insertion sex with at least three men in the past six months, 61 (19.7%) had two or more regular male sexual partners, 140 (45.3%) used condoms on >80% occasions and 34 (11.0%) occasionally or never used them during vaginal sex in the past six months. CONCLUSION: MSM in the city showed the characteristics of younger age, higher education, stable employment and income, more than one sexual partner, high frequency of high-risk behavior, and negligence of condom-use, and most (96.8%) of them are willing or very willing to obtain AIDS prevention knowledge, which deserves particular attention from relevant institutions.

[A new mutation in the GJB1 gene of a Chinese family with Charcot-Marie-Tooth disease associated with vocal cord paresis].

OBJECTIVE: To report an X-linked dominant Charcot-Marie-Tooth disease (CMTX) Chinese family with vocal cord paresis and to identify the mutation of gap junction protein beta 1 gene (GJB1). METHODS: Part of the family members with dysphagia, dysphonia and lethal respiratory failure were studied through flexible laryngoscope, clinical, brain MRI and electrophysiological examinations. After excluding large fragment tandem duplication containing peripheral myelin protein 22 gene (PMP22), direct sequencing was performed to analyze the mutation of the GJB1 gene in 5 patients including the proband, 5 unaffected family members and 50 unrelated healthy individuals. RESULTS: Eight members spanning 3 generations in this family were affected with CMTX characterized by progressive atrophy and weakness of the anterior tibial and peroneal muscles, especially in the proband. Vocal cord paresis was observed through flexible laryngoscope in total of 4 affected members with dysarthria and dysphagia, 2 of them died of severe respiratory failure due to complete bilateral vocal cord involvement. Normal brain MRI was observed in the proband. The electrophysiological data showed predominant demyelization involving the motor and sensory nerves in the proband. DNA sequencing revealed a de novo c.186 C>G missense mutation in exon 2 of the GJB1 gene, the mutation cosegregated with phenotype. CONCLUSION: Respiratory failure associated with vocal cord involvement may be a rare and severe symptom in CMTX. The present report provides further evidence for clinical and genetic heterogeneity in the X-linked Charcot-Marie-Tooth disease.