CD4/CD8 Ratio: An Independent Predictor of Herpes Zoster in Patients With Autoimmune Inflammatory Rheumatic Diseases.

BACKGROUND: A higher incidence of herpes zoster (HZ) was found in people with decreased cell-mediated immunity. However, the relationship between cellular immunity and HZ infection in patients with autoimmune inflammatory rheumatic diseases (AIRD) remains elusive. OBJECTIVE: To investigate the role of CD4/CD8 ratio in patients with AIRD and HZ. METHODS: This case-control study compared AIRD patients with and without HZ. We chose 70 AIRD patients with HZ as the experimental group and 140 AIRD patients without HZ as the control group. The clinical and laboratory findings were assessed in each trial participant. RESULTS: The CD4/CD8 ratio (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.10-0.49) was independently associated with the occurrence of HZ after adjusting for various confounders. Nonlinear analysis has unveiled a more profound nonlinear relationship between the CD4/CD8 ratio and the occurrence of HZ in patients with AIRD. The OR of HZ increased with a decreasing CD4/CD8 ratio before the turning point of 2. The adjusted regression coefficient was 0.14 (95% CI, 0.05-0.37, p<0.0001) for CD4/CD8 ratio less than 2. CONCLUSION: The CD4/CD8 ratio was expected to be a very promising quantitative biomarker for predicting the risk of developing HZ in patients with AIRD.

GPR55 activation improves anxiety- and depression-like behaviors of mice during methamphetamine withdrawal.

Methamphetamine is a potent and highly addictive neurotoxic psychostimulant that triggers a spectrum of adverse emotional responses during withdrawal. G-protein coupled receptor 55 (GPR55), a novel endocannabinoid receptor, is closely associated with mood regulation. Herein, we developed a murine model of methamphetamine-induced anxiety- and depressive-like behavior during abstinence which showed a decreased GPR55 expression in the hippocampus. Activation of GPR55 mitigated these behavioral symptoms, concomitantly ameliorating impairments in hippocampal neurogenesis and reducing neuroinflammation. These findings underscore the pivotal role of GPR55 in mediating the neuropsychological consequences of methamphetamine withdrawal, potentially via mechanisms involving the modulation of hippocampal neurogenesis and inflammation.

Interfering with reconsolidation by rimonabant results in blockade of heroin-associated memory.

Drug-associated pathological memory remains a critical factor contributing to the persistence of substance use disorder. Pharmacological amnestic manipulation to interfere with drug memory reconsolidation has shown promise for the prevention of relapse. In a rat heroin self-administration model, we examined the impact of rimonabant, a selective cannabinoid receptor indirect agonist, on the reconsolidation process of heroin-associated memory. The study showed that immediately administering rimonabant after conditioned stimuli (CS) exposure reduced the cue- and herion + cue-induced heroin-seeking behavior. The inhibitory effects lasted for a minimum of 28 days. The effect of Rimonabant on reduced drug-seeking was not shown when treated without CS exposure or 6 hours after CS exposure. These results demonstrate a disruptive role of rimonabant on the reconsolidation of heroin-associated memory and the therapeutic potential in relapse control concerning substance use disorder.

Factors affecting different COVID-19 outcomes in patients with systemic lupus erythematosus during the second pandemic wave of COVID-19 in China.

OBJECTIVE: To investigate characteristics associated with different COVID-19 outcomes of people with systemic lupus erythematosus (SLE) and COVID-19 during the second pandemic wave of COVID-19 in China. METHODS: In this retrospective study, people with SLE and COVID-19 who visited the First Affiliated Hospital of Nanchang University from December 2022 and February 2023 were subjected to this study. The three possible outcomes were listed in order of ordinal severity: (1) not hospitalized, (2) hospitalized but not receiving oxygenation, and (3) hospitalized with any ventilation or oxygenation. A multivariable ordinal logistic regression model was built to examine the association between COVID-19 severity and demographic traits, medications, comorbidities, and disease activity. Furthermore, among the 301 SLE patients included in our study, only two patients experienced mortality. In order to maintain statistical rigor, we have included these two deceased patients in the outcome measure of hospitalized with any ventilation or oxygenation. RESULTS: A total of 301 patients with SLE were enrolled in this study. The multivariate ordinal logistic regression analyses indicated that high SLE disease activity (vs remission; OR 39.04, 95% CI 3.08 to 494.44, p = .005) was associated with more severe outcomes. Three doses of COVID-19 vaccination (OR 0.19, 95% CI 0.07 to 0.51, p = .001), glucocorticoids dose (1-5 mg/day 0.14, 0.03 to 0.73, p = .020, and 6-9 mg/day 0.12, 0.02 to 0.61, p = .010), and more intensive immunosuppression drugs (0.34, 0.12 to 0.97, p = .044) were associated with better outcomes. In age-adjusted and sex-adjusted models, telitacicept (6.66, 1.35 to 32.86, p = .020) and rituximab (7.81, 1.87 to 32.66, p = .005) were associated with more severe outcomes. Hydroxychloroquine (0.47, 0.25 to 0.88, p = .018) was associated with favorable outcomes. CONCLUSION: Different COVID-19 outcomes in people with SLE are mostly driven by COVID-19 vaccination, medications, and activity SLE. More importantly, three doses of COVID-19 vaccination may be associated with better outcomes.

Eye signs as a novel risk predictor in pulmonary arterial hypertension associated with systemic lupus erythematosus.

OBJECTIVE: To investigate the role of eye signs in predicting poor outcomes in systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH). METHODS: This prospective observational study recruited patients diagnosed with SLE-PAH from Jan. 2021 to Dec. 2021 at the First Affiliated Hospital of Nanchang University; those with other potential causes of PAH were excluded. The evaluation of various parameters, such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP), 6-minute walking distance (6MWD), World Health Organization functional class (WHO-FC), echocardiography, and risk stratification based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines, was conducted at intervals of every 1-3 months, and a 6-month follow-up period was observed. The primary outcome measure considered improvement if there was a decline in the risk stratification grade at the end point and unimproved if there was no decline. Conjunctival microvascular images were observed and recorded. RESULTS: A total of 29 SLE-PAH patients were enrolled, comprising 12 in the improved group and 17 in the nonimproved group. All SLE-PAH patients showed various manifestations of eye signs, including vessel twisting, dilation, ischaemic areas, haemorrhages, reticulum deformity, and wound spots. The nonimproved group exhibited significantly lower vessel density (VD) and microvascular flow index (MFI) of conjunctival microvascular images than the improved group. Correlation analysis revealed that VD displayed a negative correlation with the WHO-FC (r = -0.413, p = 0.026) and NT-proBNP (r = -0.472, p = 0.010), as well as a positive correlation with the 6MWD (r = 0.561, p = 0.002). Similarly, MFI exhibited a negative correlation with WHO-FC (r = -0.408, p = 0.028) and NT-proBNP (r = -0.472, p = 0.010) and a positive correlation with 6MWD (r = 0.157, p = 0.004). Multivariate logistic regression analysis indicated that VD (OR 10.11, 95% CI 1.95-52.36), MFI (OR 7.85, 95% CI 1.73-35.67), NT-proBNP, and 6MWD were influential factors in predicting the prognostic improvement of SLE-PAH patients. ROC curve analysis demonstrated that VD, MFI, 6MWD, and NT-proBNP (with respective AUC values of 0.83, 0.83, 0.76, and 0.90, respectively) possessed a sensitivity and specificity of 75 and 100%, as well as 83 and 100%, respectively. Regarding prognostic prediction, VD and MFI exhibited higher sensitivity than 6MWD, whereas MFI displayed higher sensitivity and specificity than NT-proBNP. CONCLUSION: SLE-PAH can lead to various conjunctival microvascular manifestations in which vascular density and microvascular flow index can be used to assess cardiopulmonary function and predict therapeutic efficacy and prognosis in SLE-PAH patients.

Single-cell transcriptomics analysis of cellular heterogeneity and immune mechanisms in neurodegenerative diseases.

Single-cell transcriptomics analysis is an advanced technology that can describe the intracellular transcriptome in complex tissues. It profiles and analyses datasets by single-cell RNA sequencing. Neurodegenerative diseases are identified by the abnormal apoptosis of neurons in the brain with few or no effective therapy strategies at present, which has been a growing healthcare concern and brought a great burden to society. The transcriptome of individual cells provides deep insights into previously unforeseen cellular heterogeneity and gene expression differences in neurodegenerative disorders. It detects multiple cell subsets and functional changes during pathological progression, which deepens the understanding of the molecular underpinnings and cellular basis of neurodegenerative diseases. Furthermore, the transcriptome analysis of immune cells shows the regulation of immune response. Different subtypes of immune cells and their interaction are found to contribute to disease progression. This finding enables the discovery of novel targets and biomarkers for early diagnosis. In this review, we emphasize the principles of the technology, and its recent progress in the study of cellular heterogeneity and immune mechanisms in neurodegenerative diseases. The application of single-cell transcriptomics analysis in neurodegenerative disorders would help explore the pathogenesis of these diseases and develop novel therapeutic methods.

Retinal and Conjunctival Vessels in the Diagnosis and Assessment of Behcet's Disease: A New Approach.

BACKGROUND AND OBJECTIVE: The study aimed to investigate the alterations of retinal and conjunctival vessels in patients with Behcet's disease (BD). PATIENTS AND METHODS: In this case-control study, 17 patients (34 eyes) diagnosed with BD and 17 healthy volunteers (34 eyes) matched by age, sex, blood pressure, and intraocular pressure were recruited. Optical coherence tomography angiography examinations were performed to calculate the vessel density of the retina and conjunctiva according to different sizes of vessels and different zones divided by three segmentation methods of the retina: hemispheric segmentation, Early Treatment Diabetic Retinopathy Study, and central annulus segmentation. RESULTS: The vessel densities of the superficial macrovascular (P = 0.050), superficial microvascular (P < 0.001), superficial total microvascular (P < 0.001), deep total microvascular (P < 0.001), and deep total microvascular (P < 0.001) were significantly lower in the BD group. The conjunctival vessel density was significantly higher in the BD group (P < 0.001). The receiver operating characteristic curve analysis showed that the area under the curve of vessel density of the superior right (0.993, 95% CI 0.980-1) and right zones (0.996, 95% CI 0.987-1) were the largest in the superficial and deep retina, respectively. Otherwise, the area under the curve of conjunctival vessel density was 0.728 (95% CI 0.607-0.848). CONCLUSIONS: In patients with BD, retinal vessel density decreases, while conjunctival vessel density increases. Optical coherence tomography angiography provides a new noninvasive and quantitative assessment for retinal and conjunctival vessels. [Ophthalmic Surg Lasers Imaging Retina 2024;55:13-21.].

Histone modifications in cocaine, methamphetamine and opioids.

Cocaine, methamphetamine and opioids are leading causes of drug abuse-related deaths worldwide. In recent decades, several studies revealed the connection between and epigenetics. Neural cells acquire epigenetic alterations that drive the onset and progress of the SUD by modifying the histone residues in brain reward circuitry. Histone modifications, especially acetylation and methylation, participate in the regulation of gene expression. These alterations, as well as other host and microenvironment factors, are associated with a serious of negative neurocognitive disfunctions in various patient populations. In this review, we highlight the evidence that substantially increase the field's ability to understand the molecular actions underlying SUD and summarize the potential approaches for SUD pharmacotherapy.

Preparation of spirodiclofen monoclonal antibody and establishment of indirect competitive enzyme-linked immunosorbent assay.

Spirodiclofen, a spirocyclic tetronic acid derivative, has excellent acaricidal effect and is used worldwide to control the majority of important mite species. For monitoring its residue in food and environmental samples, two haptens containing different spacer arms were synthesized, a monoclonal antibody (mAb 5A4) against spirodiclofen was prepared, and a heterologous indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was established. The 50% inhibition concentration (IC50) of ic-ELISA was 25.46 ng/mL, and the working range was 5.59-133.85 ng/mL. The ic-ELISA showed no cross-reactivity with structural analogs of spirodiclofen and other commonly-used acaricides. The average recoveries from Shiranui citrus samples and Yangtze River water were 85.62%-97.74% and 85.95%-99.30%, respectively. In the analysis of 12 citrus samples, the results of the ic-ELISA were quite similar to those of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Hence, the new immunosorbent assay provides a substitute method for the qualitative and quantitative of spirodiclofen in food and environmental samples.

The Function of Retinal Thickness and Microvascular Alterations in the Diagnosis of Systemic Sclerosis.

In this study, we aim to investigate retinal thickness (RT) and superficial vascular density (SVD) differences between patients with systemic sclerosis (SSc) and healthy controls (HCs) by optical coherence tomography angiography (OCTA). Sixteen patients with a definitive SSc diagnosis without clinical signs of retinopathy and 16 normal control subjects were recruited. All individuals underwent OCTA scanning to assess macular RT and SVD. We divided each image into nine subregions as the early treatment diabetic retinopathy study (ETDRS). Visual acuity (VA) was considerably different between patients with SSc (32 eyes) and control subjects (32 eyes) (p < 0.001). Compared to the control group, individuals with SSc had decreased inner RT in inner superior, outer superior, outer temporal, inner temporal, center, and inner nasal regions (p < 0.05). Outer RT was decreased in the outer and inner temporal regions, and full RT was decreased in the regions of outer superior, inner superior, inner temporal, and outer temporal, in comparison to the control group (p < 0.05). Patients with SSc had significant reduction of SVD in the inner and outer of both superior and temporal, besides outer nasal regions than controls. (p < 0.05). Moreover, SVD was significantly associated with the outer temporal region of patients suffering from SSc (p < 0.05). Diagnostic Sensitivity of RT and SVD of Inner Superior Regions in SSc, as indicated by areas under curves of the Receiver Operating Characteristic (ROC), were 0.874 (95% CI: 0.786-0.962) and 0.827 (95% CI: 0.704-0.950), respectively. In conclusion, VA may be affected by RT variations inside the macula in patients with SSc. Measuring RT with OCTA could be a useful predictor of early diagnosis.

Genus Tetrastigma: A review of its folk uses, phytochemistry and pharmacology.

The genus Tetrastigma belongs to the Vitaceae family and contains over 100 species. This paper reviewed folk uses, chemical constituents, pharmacological activities, and clinical applications of the medicinal plants in the genus Tetrastigma. In addition, the paper also discussed the current problems for the further studies. Up to now, more than 240 compounds were reported from the genus Tetrastigma, covering 74 flavonoids, 14 terpenoids, 19 steroids, 21 phenylpropanoids, 14 alkaloids and others constituents. Among them, flavonoids are the major and the characteristic chemical constituents in this genus. Modern pharmacological studies and clinical practice showed that the extracts and chemical constituents of Tetrastigma species possessed wide pharmacological activities including antitumor, antioxidative, hepatoprotective, antiviral, anti-inflammatory, and analgesic activities. The information summarized in this paper provides valuable clues for new drug discovery and an incentive to expand the research of genus Tetrastigma.

Blockade of exosome generation by GW4869 inhibits the education of M2 macrophages in prostate cancer.

BACKGROUND: Tumor-associated macrophages are considered to be a major contributor affecting the development of tumors. Recently, numerous studies have shown that tumor cells were able to educate their microenvironment by delivering a significant amount of exosomes, however, the mechanism that exosomes from PCa cells work in macrophage polarization remains obscure. Therefore, we sought to determine whether blockade of exosome generation by GW4869, an inhibitor of exosome biogenesis, would impede macrophages from differentiating into M2 cells. RESULTS: In this study, we first obtained exosomes from the supernatant media of PCa cells cultured with exosome-free serum using the Magcapture™ Exosome Isolation Kit PS, and then investigated their effects on macrophages. Our data confirmed that exosomes released by prostate cancer cells can induce macrophages to differentiate into M2 cells. Mechanistically speaking, exosomes exert their effects on macrophages through activating the AKT and STAT3 signaling pathways. Importantly, treatment with GW4869 significantly inhibited the release of exosomes from PCa cells, and further impaired M2 differentiation of macrophages and their pro-tumor activity. We also demonstrated that GW4869 was able to inhibit the education of M2 macrophages, and then inhibit the progression of prostate cancer in vivo. CONCLUSIONS: In brief, our findings indicated that GW4869 impeded the PCa exosome-induced M2 differentiation of macrophages and the progression of prostate cancer, suggesting that GW4869 could play an important role in the treatment of prostate cancer metastasis as an inhibitor of tumor exosome secretion.