Efficacy and prognostic value of peripheral blood CD4+ T cells and serum IL-6 and IL-8 in tuberculous meningitis.

Objective: To investigate the value of peripheral blood clusters of differentiation 4 (CD4+) T-lymphocyte (T cells) count and serum interleukin-6 (IL-6) and interleukin-8 (IL-8) in the treatment and prognosis of tuberculous meningitis (TBM). Methods: Sixty-five patients with TBM were prospectively included in the observation group. Sixty-five patients with pulmonary TB and a group of 65 healthy individuals served as the control groups. The differences in peripheral blood CD4+ T-cell count, serum IL-6, and IL-8 levels were compared, and changes in these indices after anti-TB treatment in the observation group were analysed. The observation group was divided into effective and ineffective groups based on their response after 24 weeks of anti-TB treatment. The study also evaluated the influence of peripheral blood CD4+ T-cell count, serum IL-6, and IL-8 levels on the adverse prognosis of TBM during anti-TB treatment. Results: Before treatment, the CD4+ T-cell count in the peripheral blood of the observation group was lower than in both the control and healthy groups, and serum IL-6 and IL-8 levels were higher than in the control group (P < 0.001). After 24 weeks of anti-TB treatment, the CD4+ T-cell count in the peripheral blood of the observation group increased, whereas the levels of IL-6 and IL-8 decreased significantly (P < 0.001). The levels of CD4+ T cells and IL-6 in the peripheral blood of patients before treatment were identified as independent factors influencing the efficacy of anti-TB treatment (odds ratio [OR] = 0.989, 95 % confidence interval [CI]: 0.980-0.997; OR = 1.010, 95 % CI: 1.003-1.017). Conclusion: In patients with TBM, the CD4+ T-cell count in the peripheral blood is decreased, whereas serum IL-6 and IL-8 are increased. The combination of CD4+ T cells and IL-8 shows a degree of predictive value for the prognosis of anti-TB treatment.

Ethnic disparities in prevalence of chronic non-communicable diseases and its multimorbidity among older adults in rural southwest China.

BACKGROUND: As the population ages, chronic non-communicable diseases (NCDs) multimorbidity has emerged as a major public health issue globally. This study examines ethnic disparities in prevalence of NCDs and its multimorbidity among rural southwest Chinese older adults. METHODS: A cross-sectional survey was conducted in rural southwest population aged ≥ 60 years consisting of 5,642 consenting participants of Han and three ethnic minority groups (Dai, Ha Ni, and Bai). Information about participants' demographic characteristics and lifestyle behaviors was obtained using a standard questionnaire. Anthropometric measurements including height, weight, and waist circumference, fasting blood sugar and blood pressure measurement, as well as post-bronchodilator spirometry test were recorded for each participant. RESULTS: The age-standardized prevalence of five common chronic NCDs- hypertension, diabetes, coronary heart disease (CHD), stroke, chronic obstructive pulmonary disease (COPD) - and its multimorbidity was 72.8%, 15.9%, 4.0%, 10.0%, 9.8%, and 27.6%, respectively. Bai participants had both the highest overall and sex-specific prevalence rates of hypertension, diabetes, stroke, and COPD, whereas Han participants had the highest rates of CHD (P < 0.01). The results of multivariate logistic regression analysis indicated that female and older participants had a higher probability of chronic NCDs multimorbidity than their counterparts (P < 0.01). Bai ethnic minority participants were more likely to have NCDs multimorbidity while Ha Ni and Dai ethnic minority participants were less likely to have NCD multimorbidity relative to the Han participants (P < 0.05). Older adults with a higher level of education and family history of chronic NCDs, and who were also current smokers, current drinkers, obese, centrally obese, and physically inactive had a greater probability of developing chronic NCDs multimorbidity (P < 0.01). CONCLUSIONS: Ethnicity and individual demographic and lifestyle factors significantly impact prevalence of chronic NCDs multimorbidity. Future chronic NCDs prevention and control strategies must be tailored to address ethnicity, and culturally tailored lifestyle interventions may reduce the prevalence of chronic NCDs multimorbidity in rural southwest China.

Inflammation markers and the risk of hypertension in people living with HIV.

Background: The incidence of hypertension is high in people living with HIV (PLWH). High-sensitivity C-reactive protein (hsCRP), systemic inflammation response index (SIRI), and neutrophil-to-monocyte ratio (NMR) are considered economic and convenient parameters that reflect the levels of inflammation in patients. Our aim was to explore whether indirect inflammation markers are associated with hypertension in PLWH. Methods: This was a case-control study. The case group (hypertension) comprised PLWH with hypertension, and the control group (non-hypertension) comprised sex- and age-(± 3 years)-matched PLWH without hypertension. Demographic parameters, hsCRP, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune- inflammation index (SII), SIRI, lymphocyte-to-monocyte ratio (LMR), platelet-to-neutrophil ratio (PNR), platelet-to-monocyte ratio (PMR), NMR, time to HIV diagnosis, antiretroviral therapy (ART) duration, recent CD4+ and CD8+ cell counts, recent CD4+/CD8+ ratio, recent HIV viral load (HIV-RNA),and recent ART regimen were obtained from the patients' electronic medical records. A t-test or Wilcoxon rank-sum test was performed to compare differences between the two groups, and conditional logistic regression was used to analyze the risk factors of hypertension. Correlations between inflammation markers and CD4+ cell counts, CD8+ cell counts, and CD4+/CD8+ ratio were analyzed using Spearman's correlation. Results: In the hypertension group, body mass index (BMI), hsCRP, NLR, SII, SIRI, NMR, time to HIV diagnosis, ART duration, CD4+ and CD8+ cell counts, and CD4+/CD8+ ratio, the ratio of HIV-RNA < 100 copies/mL were all higher than those in the non-hypertension group, while the PNR was lower than that in the non-hypertension group. ART duration, CD4+ cell counts, HIV-RNA < 100 copies/mL, hsCRP, SIRI, and NMR were positively associated with hypertensive risk in PLWH. CD8+ cell counts and CD4+/CD8+ ratio was negatively associated with hypertensive risk in PLWH. SIRI was negatively correlated with CD4+ cell counts and CD8+ cell counts, but positively correlated with CD4+/CD8+ ratio. Conclusions: We identified positive associations between inflammation markers hsCRP, SIRI, NMR and hypertensive risk in PLWH. Alleviating inflammation may help control or delay the occurrence of hypertension in PLWH.

Transcriptomic Profiling Reveals Underlying Immunoregulation Mechanisms of Resistant Hypertension in Injection Drug Users.

Background: Hypertension is a common complication in injection drug users (IDU), especially a high proportion of resistant hypertension occurs among them. However, the involving mechanisms remain largely unknown. Methods: We here investigated the key signaling moieties in resistant hypertension in drug users. Analyses were performed with high-throughput transcriptomic sequencing data of peripheral blood from individuals with drug-sensitive hypertension (Ctrl-DS), IDU with resistant hypertension (IDU-DR), and IDU with sensitive hypertension (IDU-DS). Results: We showed that 17 and 1 genes in IDU-DS, 48 and 4 genes in IDU-DR were upregulated and downregulated compared Ctrl-DS, and 2 and 4 genes were upregulated and downregulated in IDU-DR compared with IDU-DS, respectively (p ≤ 0.01 and |log2(FC)| ≥ 1). Differentially expressed genes (DEGs) between Ctrl-DS and IDU-DS were mainly involved in Gene ontology terms of immunoglobulin complex and blood microparticle. DEGs between IDU-DS and IDU-DR were mainly involved in immune system process and immunoglobulin complex. DEGs between Ctrl-DS and IDU-DR were mainly involved in immunoglobulin complex, blood microparticle and cytoplasmic vesicle lumen. We identified 2 gene clusters (brown modules, MEbrown; turquoise module, MEturquoise) correlated with IDU-DR and a gene cluster (magenta module, MEmagenta) correlated with IDU-DS by weighted gene co-expression network analysis (WGCNA). Functional analysis demonstrated that pathways of focal adhesion and focalin-1-rich granule lumen were involved in the development of IDU-DR, and the cytosolic large ribosomal subunit may relate to IDU-DR. Further, immune cell infiltration analysis demonstrated that the abundance of dendritic cells (DCs), natural Treg cells (nTreg), and exhausted T cells (Tex) in IDU-DR and IDU-DS, naïve CD8+ T cells in IDU-DS was significantly different compared with that in Ctrl-DS. The abundance of cytotoxic T cells (Tc) was significantly different between IDU-DS and IDU-DR. Conclusion: Our findings indicated a potential function of immunoregulation mechanisms for resistant hypertension.

Dynamic transcriptome landscape of Paragonimus proliferus developmental stages in the rat lungs.

Paragonimus proliferus, a lung fluke of the genus Paragonimus, was first reported in Yunnan province, China. P. proliferus can infect Sprague-Dawley (SD) rats and cause lung damage, but there is still no direct evidence of human infection. Until now, there has been a lack of studies on P. proliferus parasitism and development in mammalian lung tissue. The aim of this study was to perform transcriptomic profiling of P. proliferus at different developmental stages. SD rats were infected with P. proliferus metacercariae obtained from crabs; worms isolated from the lungs at different time points as well as metacercariae were subjected to whole transcriptome sequencing. Overall, 34,403 transcripts with the total length of 33,223,828 bp, average length of 965 bp, and N50 of 1833 bp were assembled. Comparative analysis indicated that P. proliferus, similar to other Paragonimus spp., expressed genes related to catabolism, whereas P. proliferus-specific transcripts were related to the maintenance of cellular redox homeostasis, sensitivity to bacteria, and immune response. Transcriptional dynamics analysis revealed that genes involved in the regulation of catabolism and apoptosis had stable expression over the P. proliferus life cycle, whereas those involved in development and immune response showed time-dependent changes. High expression of genes associated with immune response corresponded to that of genes regulating the sensitivity to bacteria and immune protection. We constructed a P. proliferus developmental model, including the development of the body, suckers, blood cells, reproductive and tracheal systems, lymph, skin, cartilage, and other tissues and organs, and an immune response model, which mainly involved T cells and macrophages. Our study provides a foundation for further research into the molecular biology and infection mechanism of P. proliferus.

New triterpenes from Cimicifuga yunnanensis down-regulating the mRNA expression of CD147, MMP-2, and MMP-9.

Eleven new 9,19-cycloartane triterpenes (1-9, 11-12) and one undescribed lanostane-type aglycone (10) were identified from the aerial parts of Cimicifuga yunnanensis. The new structures were elucidated by analysis of spectroscopic data. Compounds 3-5, 7-9, and 11, without obvious cytotoxicity at 50 µM, were evaluated for inhibiting the mRNA expressions of atherosclerosis-related factors of CD147 (extracellular matrix metalloproteinase inducer, EMMPRIN), matrix metalloproteinase 2 (MMP-2) and MMP-9 in phorbol-12-myristate-13-acetate (PMA) induced Human monocytic THP-1 cells by using a quantitative real-time PCR method (q-PCR). Among them, aglycones 7 and 8 showed potent activities, whereas all tested glycosides were inactive. Compounds 7 and 8 suppressed the mRNA expression of CD147 in a dose-dependent manner, with an IC50 value of 3.38 ± 0.27 µM and 8.25 ± 0.33 µM, respectively. Besides, 7 dose-related down-regulated the mRNA expression of MMP-2, and MMP-9, having an IC50 value of 6.32 ± 0.31 µM and 11.57 ± 0.23 µM, respectively. Meanwhile, 8 at 10 µM reduced the mRNA expression of MMP-2 and MMP-9 by 35% and 25%, respectively. Significantly, the migration ability of the induced THP-1 cells was potently and dose-dependently inhibited by 7, with an IC50 value of 5.87 ± 0.27 µM.

Effects of Short-Term Low-Dose Glucocorticoids for Patients with Mild COVID-19.

OBJECTIVES: To evaluate the role of short-term low-dose glucocorticoids in mild COVID-19 patients. METHODS: We conducted a retrospective, cross-sectional, single-center study in Kunming, China. A total of 33 mild COVID-19 cases were divided into two treatment groups (with and without glucocorticoids, methylprednisolone, were used in this setting), and the absolute value of peripheral blood lymphocyte count; CD3+, CD4+, and CD8+ T cell counts; and the time to achieve negative transformation of a nucleic acid pharyngeal swab were recorded. Peripheral blood lymphocyte and T cell counts were compared between the treatment group and 25 healthy individuals. At the point of time when there was a 50% accumulation conversion rate (positive to negative nucleic acid on pharyngeal swab), and the nucleic acid turned negative in half of the patients in two groups, the peripheral blood lymphocyte and T cell counts were compared between treatment groups. RESULTS: The mean cumulative time for the 50% negative conversion rate of the nucleic acid in the pharyngeal swab was 17.7 ± 5.1 days and 13.9 ± 5.4 days in the glucocorticoid group and the nonglucocorticoid group, respectively. The absolute peripheral blood lymphocyte count and the T cell subset count in the glucocorticoid group were lower than those in the nonglucocorticoid group. When the nucleic acid turned negative in half of the patients, the absolute value of peripheral blood lymphocyte count and CD4+ T cells of the glucocorticoid group and the nonglucocorticoid group was not significantly different; the CD3+ and CD8+ T cells in the glucocorticoid group were lower than those in the nonglucocorticoid group. The absolute peripheral blood lymphocyte count, CD3+ T cells, and CD4+ T cells in the glucocorticoid group were lower than those of the healthy group during the whole disease period, and CD8+ T cells returned to normal at 19-21 days of the disease period. There was no significant difference between the nonglucocorticoid group and the healthy group for absolute peripheral blood lymphocyte and CD8+ T cells; moreover, CD3+ T cells and CD4+ T cells were lower in the nonglucocorticoid group than those in the healthy group from the day of admission to the 18th day and returned to normal at the period of 19-21 days. The absolute peripheral lymphocyte count (P = 0.048, effect size d = 0.727) and T cell subset count (CD3: P = 0.042, effect size d = 0.655; CD4: P < 0.01, effect size d = 0.599; and CD8: P = 0.034, effect size d = 0.550) in the nonglucocorticoid group were higher than those in the glucocorticoid group, and the difference between the groups was statistically significant. CONCLUSIONS: This study found that the use of short-term, low-dose glucocorticoids does not negatively influence the clinical outcome, without affecting the final clearance of viral nucleic acid in mild COVID-19 patients.