Approximately 15-20% of COVID-19 patients will develop severe pneumonia, about 10 % of which will die if not properly managed. Earlier discrimination of the potential severe patients basing on routine clinical and laboratory changes and commencement of prophylactical management will not only save their lives but also mitigate the otherwise overwhelmed health care burden. In this retrospective investigation, the clinical and laboratory features were collected from 125 COVID-19 patients, who were classified into mild (93 cases) or severe (32 cases) groups according to their clinical outcomes after 3 to 7-days post-admission. The subsequent analysis with single-factor and multivariate logistic regression methods indicated that 17 factors on admission differed significantly between mild and severe groups, but that only comorbid with underlying diseases, increased respiratory rate (>24/min), elevated C-reactive protein (CRP >10mg/liter), and lactate dehydrogenase (LDH >250U/liter), were independently associated with the later disease development. Finally, we evaluated their prognostic values with the receiver operating characteristic curve (ROC) analysis and found that the above four factors could not confidently predict the occurrence of severe pneumonia individually, but that a combination of fast respiratory rate and elevated LDH significantly increased the predictive confidence (AUC= 0.944, sensitivity= 0.941, and specificity= 0.902). A combination consisting of 3- or 4-factors could further increase the prognostic value. Additionally, measurable serum viral RNA post-admission independently predicted the severe illness occurrence. In conclusion, a combination of general clinical characteristics and laboratory tests could provide high confident prognostic value for identifying potential severe COVID-19 pneumonia patients. Summary: With our successful experience of treating COVID-19 patients, we retrospectively found that routine clinical features could reliably predict severe pneumonia development, thus provide quick and affordable references for physicians to save the otherwise fatal patients with the limited medical resource.

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with age. A wealth of evidence indicates that the amyloid β (Aβ) aggregates result from dyshomeostasis between Aβ production and clearance, which plays a pivotal role in the pathogenesis of AD. Consequently, therapies targeting Aβ reduction represent a promising strategy for AD intervention. Tetramethylpyrazine nitrone (TBN) is a novel tetramethylpyrazine derivative with potential for the treatment of AD. Previously, we demonstrated that TBN markedly enhanced cognitive functions and decreased the levels of Aβ, APP, BACE 1, and hyperphosphorylated tau in 3×Tg-AD mice. However, the mechanism by which TBN inhibits Aβ deposition is still unclear. In this study, we employed APP/PS1 mice treated with TBN (60 mg/kg, ig, bid) for six months, and N2a/APP695swe cells treated with TBN (300 μM) to explore the mechanism of TBN in Aβ reduction. Our results indicate that TBN significantly alleviated cognitive impairment and reduced Aβ deposition in APP/PS1 mice. Further investigation of the underlying mechanisms revealed that TBN decreased the expression of APP and BACE1, activated the AMPK/mTOR/ULK1 autophagy pathway, inhibited the PI3K/AKT/mTOR/ULK1 autophagy pathway, and decreased the phosphorylation levels of JNK and ERK in APP/PS1 mice. Moreover, TBN was found to significantly reduce the mRNA levels of APP and BACE1, as well as those of SP1, CTCF, TGF-β, and NF-κB, transcription factors involved in regulating gene expression. Additionally, TBN was observed to decrease the level of miR-346 and increase the levels of miR-147 and miR-106a in the N2a/APP695swe cells. These findings indicate that TBN may reduce Aβ levels likely by reducing APP expression by regulating APP gene transcriptional factors and miRNAs, reducing BACE1 expression, and promoting autophagy activities.

Background: Sepsis contributes to global mortality due to chronic immunodeficiency and metabolic disturbances, particularly in those infected with the human immunodeficiency virus (HIV). The TyG index and CD4 ⁺ T-cell count individually predict sepsis outcomes, but reflect different biological aspects. The benefit of integrating these markers for risk stratification in patients with HIV-associated sepsis remains unclear. This study aimed to assess whether combining the TyG index, a surrogate for insulin resistance, with CD4 ⁺ T cell count enhanced early prediction of 28-day mortality risk in adults hospitalized with HIV-associated sepsis. Methods: Clinical data were retrospectively collected from patients admitted to the Eighth Affiliated Hospital of Guangzhou Medical University. The participants were stratified into four risk categories according to their TyG index and CD4 ⁺ T cell count. The primary outcome was 28-day all-cause mortality, and secondary outcomes were 7-day and in-hospital all-cause mortality. Survival across strata was compared using the Kaplan–Meier analysis and the log-rank test; associations were determined using multivariate Cox proportional hazards models. Independent predictors of death were ranked using the Boruta feature selection algorithm. In a nested sub-cohort of 155 patients, plasma concentrations of 13 inflammatory cytokines were quantified using the LEGENDplex Human Inflammation Panel 1. Results: Among 1,278 patients with HIV-associated sepsis, 847 had CD4 counts <50 cells/μL. The Kaplan–Meier analysis revealed progressively higher 7-day and 28-day all-cause mortality rates across these strata, with the highest mortality in the low CD4 ⁺ and high TyG groups. A multivariable Cox regression analysis, adjusted for multiple covariates, indicated an elevated risk of 28-day mortality in patients with low CD4 and high TyG compared to those with high CD4 and low TyG. Similar trends were observed for 7-day and in-hospital mortality. The Boruta algorithm identified combined TyG-CD4 as an important predictor. The immunological sub-study demonstrated significant differences in cytokine profiles among the risk groups, with the low CD4 and high TyG groups exhibiting a specific inflammatory response. Conclusion: A combined TyG-CD4 assessment provides a rapid and straightforward means of integrating metabolic and immunological insights to identify high-risk individuals early, thereby generating hypotheses for future trials of personalized therapeutic strategies.

The COVID-19 pandemic has highlighted the urgent need for accurate, rapid, and cost-effective diagnostic methods to identify and track the disease. Traditional diagnostic methods, such as PCR and serological assays, have limitations in terms of sensitivity, specificity, and timeliness. To investigate the potential of using protein–peptide hybrid microarray (PPHM) technology to track the dynamic changes of antibodies in the serum of COVID-19 patients and evaluate the prognosis of patients over time. A discovery cohort of 20 patients with COVID-19 was assembled, and PPHM technology was used to track the dynamic changes of antibodies in the serum of these patients. The results were analyzed to classify the patients into different disease severity groups, and to predict the disease progression and prognosis of the patients. PPHM technology was found to be highly effective in detecting the dynamic changes of antibodies in the serum of COVID-19 patients. Four polypeptide antibodies were found to be particularly useful for reflecting the actual status of the patient’s recovery process and for accurately predicting the disease progression and prognosis of the patients. The findings of this study emphasize the multi-dimensional space of peptides to analyze the high-volume signals in the serum samples of COVID-19 patients and monitor the prognosis of patients over time. PPHM technology has the potential to be a powerful tool for tracking the dynamic changes of antibodies in the serum of COVID-19 patients and for improving the diagnosis and prognosis of the disease.

Our patient, a 48-year-old man from Guangdong’s coastal region, worked selling and processing oysters and other seafood. He started experiencing swelling and pain in his left knee on October 4, 2022, and they got worse over time. The findings of mNGS test showed Vibrio vulnificus infection. The patient had AIDS, hepatitis A and hepatitis B concurrently. He was admitted to the hospital’s intensive care unit (ICU) for treatment as his symptoms worsened. We refrained from performing an amputation because the family members expressed a desire to keep the limb. The limb was managed with regular dressing changes, thorough debridement, wound closure, ongoing VSD drainage, and local antibiotic irrigation. The patient’s organ function eventually returned to normal, and the systemic infection got better. On November 1, the wound’s new granulation tissue had grown well and had gradually crept to cover 80% of the wound. The tissue’s blood flow had also improved, indicating a trend of growth and healing.

Alzheimer’s disease (AD) is an age-associated neurodegenerative disorder. A wealth of evidence indicates that the amyloid β (Aβ) aggregates result from dyshomeostasis between Aβ production and clearance, which plays a pivotal role in the pathogenesis of AD. Consequently, therapies targeting Aβ reduction represent a promising strategy of AD intervention. Tetramethylpyrazine nitrone (TBN) is a novel tetramethylpyrazine derivative with the potential for the treatment of AD. Previously, we demonstrated that TBN markedly improved cognitive functions and reduced Aβ, APP, BACE 1 and hyperphosphorylated tau levels in 3 × Tg-AD mice. However, the mechanism by which TBN inhibits Aβ deposition still unclear. In this study, we employed the APP/PS1 mice treated with TBN (60 mg/kg, ig, bid) for six months and N2a/APP695swe cells treated with TBN (300 μM) to explore the mechanism of TBN on the Aβ reduction. Our results indicated that TBN significantly alleviated cognitive impairment and reduced Aβ depositions in APP/PS1 mice. Further investigation of the underlying mechanisms revealed that TBN decreased the expression of APP and BACE1, activated the AMPK/mTOR/ULK1 autophagy pathway and inhibited the PI3K/AKT/mTOR/ULK1 autophagy pathway, as well as decreased the phosphorylation levels of JNK and ERK in APP/PS1 mice. Moreover, TBN was found to significantly reduce the mRNA levels of APP and BACE1, as well as those of SP1, CTCF, TGF-β, and NF-κB, transcription factors involved in regulating gene expression. Additionally, TBN was observed to decrease the level of miR-346 and increase the levels of miR-147 and miR-106a in the N2a/APP695swe cells. These findings indicate that TBN may reduce Aβ levels likely via reducing APP expression by regulating APP gene transcriptional factors and miRNAs, reducing BACE1 expression, and promoting autophagy activities.