Sweat as a source of non-invasive biomarkers for clinical diagnosis: An overview.

Sweat has excellent potential as one of the sources of non-invasive biomarkers for clinical diagnosis. It is relatively easy to collect and process and may contain different disease-specific markers and drug metabolites, making it ideal for various clinical applications. This article discusses the anatomy of sweat glands and their role in sweat production, as well as the history and development of multiple sweat sample collection and analysis techniques. Another primary focus of this article is the application of sweat detection in clinical disease diagnosis and other life scenarios. Finally, the limitations and prospects of sweat analysis are discussed.

Association between corticosteroid use and 28-day mortality in septic shock patients with gram-negative bacterial infection: a retrospective study.

Purpose: Although corticosteroids are recommended in the 2021 Surviving Sepsis Campaign (SSC) guidelines, evidence with respect to their effects on short-term mortality remains conflicting. We conducted this study to identify whether corticosteroids alter 28-day mortality in septic shock patients with gram-negative bacterial infection. Materials and methods: A total of 621 patients with septic shock and gram-negative bacterial culture results were identified from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching (PSM) was performed, and Kaplan-Meier survival curve analyses with log-rank tests were used to determine the relationship between corticosteroid use and the risk of 28-day mortality. Subgroup analyses were conducted to assess whether the conclusions were stable and reliable. Results: Corticosteroid administration was associated with increased 28-day mortality in septic shock patients with gram-negative bacterial infection (log-rank test P = 0.028). The incidence of Stage 2 or 3 AKI and the rate of hospital mortality were higher among patients who received corticosteroids. The incidence of Stage 2 or 3 AKI in the early period significantly mediated the relationship between corticosteroid use and 28-day mortality [P =0.046 for the average causal mediation effect (ACME)]. Interaction tests indicated that the effect of corticosteroid use was maintained in patients with a neutrophil-to-lymphocyte ratio (NLR) of <20 (P-value for interaction = 0.027). Conclusion: Systemic corticosteroid use could be harmful in septic shock patients with gram-negative bacterial infection, especially in patients with relatively low NLR.

Real-world study of PD-1/L1 immune checkpoint inhibitors for advanced non-small cell lung cancer after resistance to EGFR-TKIs.

Background: Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) inhibitors have achieved good efficacy and safety in patients with advanced EGFR mutation-negative non-small cell lung cancer (NSCLC), but their efficacy in patients with previous EGFR mutations is limited. The aim of the present study was to explore the efficacy of PD-1/L1 immune checkpoint inhibitors for the treatment of patients with advanced NSCLC who are resistant to EGFR-TKIs. Methods: This retrospective study included 123 patients with stage IV NSCLC who received treatment in Shanghai Changzheng Hospital between January 2019 and January 2022 after failure of first-line EGFR-TKIs. Of them, 39 received ICIs + chemotherapy and anti-angiogenic drugs (ICIs+BCP group), 51 received ICIs monotherapy (ICIs group), and 33 received chemotherapy and anti-angiogenic drugs (BCP group). The gender, age, smoking history, ECOG score, EGFR mutation type, PD-L1 TPS expression, and the first routine blood index before second-line treatment of all enrolled patients were recorded, and their clinical outcomes and prognosis factors were analyzed. Results: There was no significant difference in the objective response rate (ORR) and disease control rate (DCR) between the three groups. Patients in ICIs+BCP group had better prognosis than those in ICIs monotherapy group (PFS:9.5 vs. 4.64 months, p<0.001; OS: 16.97 vs. 7.9 months p<0.001) or BCP group (9.5 vs. 6.48 months, p<0.005; OS: 16.97 vs. 11.39 months p<0.005). Conclusion: Our findings suggest that in the real-world practice in China, PD-1/L1 immune checkpoint inhibitors combined with chemotherapy and anti-angiogenic drugs are effective for the treatment of patients with advanced NSCLC who are resistant to EGFR-TKIs.

Association between previous cataract surgery and cognition among middle-aged and older Chinese: the China health and retirement longitudinal study (CHARLS).

BACKGROUND: Cataract is the primary cause of blindness globally, and surgery offers the only method by which to remove cataracts. We aimed to examine whether previous cataract surgery is associated with cognitive function. METHODS: Our study included 13,824 participants. Data from the baseline of the China Health and Retirement Longitudinal Study (CHARLS) were used. The participants were categorized into two groups: with and without previous cataract surgery. Weighted multiple linear regression was used to obtain the ß and 95% confidence intervals (CI). RESULTS: The participants who had previous cataract surgery (n = 261) scored lower in cognition, including both memory and mental state, than those without previous cataract surgery. After adjusting for socioeconomic factors and metabolic measures, a negative association was evident between previous cataract surgery and cognition (ß = -0.647, 95% CI: -1.244, - 0.049). Furthermore, the participants who were older and female demonstrated a decline in cognition, while living in cities and having higher levels education were associated with higher cognition. CONCLUSIONS: Better cognitive function was associated with less previous cataract surgery or cataract occurrence. This suggests that a period of vision loss due to cataract leads to cognitive decline, however further studies are need to dissect the impact of vision loss and cataract surgery on cognitive decline.

Single-Cell Transcriptomics Uncover Key Regulators of Skin Regeneration in Human Long-Term Mechanical Stretch-Mediated Expansion Therapy.

Tissue expansion is a commonly performed therapy to grow extra skin in vivo for reconstruction. While mechanical stretch-induced epidermal changes have been extensively studied in rodents and cell culture, little is known about the mechanobiology of the human epidermis in vivo. Here, we employed single-cell RNA sequencing to interrogate the changes in the human epidermis during long-term tissue expansion therapy in clinical settings. We also verified the main findings at the protein level by immunofluorescence analysis of independent clinical samples. Our data show that the expanding human skin epidermis maintained a cellular composition and lineage trajectory that are similar to its non-expanding neighbor, suggesting the cellular heterogeneity of long-term expanded samples differs from the early response to the expansion. Also, a decrease in proliferative cells due to the decayed regenerative competency was detected. On the other hand, profound transcriptional changes are detected for epidermal stem cells in the expanding skin versus their non-expanding peers. These include significantly enriched signatures of C-FOS, EMT, and mTOR pathways and upregulation of AREG and SERPINB2 genes. CellChat associated ligand-receptor pairs and signaling pathways were revealed. Together, our data present a single-cell atlas of human epidermal changes in long-term tissue expansion therapy, suggesting that transcriptional change in epidermal stem cells is the major mechanism underlying long-term human skin expansion therapy. We also identified novel therapeutic targets to promote human skin expansion efficiency in the future.

Associations of sensory impairment and cognitive function in middle-aged and older Chinese population: The China Health and Retirement Longitudinal Study.

BACKGROUND: Little is known about the associations between vision impairment, hearing impairment, and cognitive function. The aim of this study was to examine whether vision and hearing impairment were associated with a high risk for cognitive impairment in middle-aged and older Chinese adults. METHODS: A total of 13 914 Chinese adults from the China Health and Retirement Longitudinal Study (CHARLS) baseline were selected for analysis. Sensory impairment was assessed from a single self-report question, and we categorized sensory impairment into four groups: no sensory impairment, vision impairment, hearing impairment, and dual sensory impairment. Cognitive assessment covered memory, mental state, and cognition, and the data was obtained through a questionnaire. RESULTS: Memory was negatively associated with hearing impairment (ß = -0.043, 95% confidence interval (CI) = -0.076, -0.043) and dual sensory impairment (ß = -0.033, 95% CI = -0.049, -0.017); mental status was negatively associated with vision impairment (ß = -0.034, 95% CI = -0.049, -0.018), hearing impairment (ß = -0.070, 95% CI = -0.086, -0.055), and dual sensory impairment (ß = -0.054, 95% CI = -0.070, -0.039); and cognition was negatively associated with vision impairment (ß = -0.028, 95% CI = -0.044, -0.013), hearing impairment (ß = -0.074, 95% CI = -0.090, -0.059), and dual sensory impairment (ß = -0.052, 95% CI = -0.067, -0.036), even after adjusting for demographics, social economic factors, and lifestyle behavior. CONCLUSIONS: Vision and hearing impairment are negatively associated with memory, mental status, and cognition for middle-aged and elderly Chinese adults. There were stronger negative associations between sensory impairment and cognitive-related indicators in the elderly compared to the middle-aged.

Hypoxia induces tumor cell growth and angiogenesis in non-small cell lung carcinoma via the Akt-PDK1-HIF1α-YKL-40 pathway.

BACKGROUND: As one of the most common forms of cancer, non-small cell lung carcinoma (NSCLC), is characterized by oxygen deprivation (hypoxia). The transcription factor hypoxia-inducible factor (HIF)-1α is a major mediator which responds hypoxia and regulates many contributing factors. The various modes of hypoxia regulation are frequently the focus of research studies. With reference to previous published research, we hypothesized that hypoxia promotes the growth and angiogenesis of NSCLC via the Akt-PDK1-HIF1α-YKL-40 pathway, and verified it. METHODS: We mainly investigated changes in related factor expression between differently treated CL1-5 cells. We carried out overexpression and underexpression transfection, Western blot, rt-PCR and ELISA, and observed cellular biological behaviors by CCK-8 migration and invasion assay, and tube formation assay. RESULTS: A hypoxic environment significantly increased the phosphorylation of Akt and PDK1 in mitochondria. The hypoxia-induced accumulation of p-Akt in mitochondria activated PDK1 phosphorylation, promoted the expression of HIF1α, and the expression of YKL-40. The overexpression of YKL-40 promoted the proliferation, migration, invasion and tubule formation of CL1-5 cells. CONCLUSIONS: A hypoxic tumor microenvironment can promote the expansion and angiogenesis of NSCLC cells through the Akt-PDK1-HIF1α-YKL-40 pathway. This may provide a new mechanism and potential interventional target for anti-vascular lung cancer therapy.