Deciphering the dynamic changes in antibodies against SARS-CoV-2 is essential for understanding the immune response in COVID-19 patients. Here we analyze the laboratory findings of 1,850 patients to ...describe the dynamic changes of the total antibody, spike protein (S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)-specific immunoglobulin M (IgM) and G (IgG) levels during SARS-CoV-2 infection and recovery. The generation of S-, RBD-, and N-specific IgG occurs one week later in patients with severe/critical COVID-19 compared to patients with mild/moderate disease, while S- and RBD-specific IgG levels are 1.5-fold higher in severe/critical patients during hospitalization. The RBD-specific IgG levels are 4-fold higher in older patients than in younger patients during hospitalization. In addition, the S- and RBD-specific IgG levels are 2-fold higher in the recovered patients who are SARS-CoV-2 RNA negative than those who are RNA positive. Lower S-, RBD-, and N-specific IgG levels are associated with a lower lymphocyte percentage, higher neutrophil percentage, and a longer duration of viral shedding. Patients with low antibody levels on discharge might thereby have a high chance of being tested positive for SARS-CoV-2 RNA after recovery. Our study provides important information for COVID-19 diagnosis, treatment, and vaccine development.
Males and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take the sex factor into consideration. We ...performed a sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and severe acute respiratory syndrome coronavirus (SARS-CoV-2) specific antibody levels of 1558 males and 1499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. The total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels were measured by chemiluminescence. We found that male patients had approximately two-fold rates of ICU admission (4.7% vs. 2.7% in males and females, respectively, P = 0.005) and mortality (3% vs. 1.4%, in males and females, respectively, P = 0.004) than female patients. Survival analysis revealed that the male sex is an independent risk factor for death from COVID-19 (adjusted hazard ratio HR = 2.22, 95% confidence interval CI: 1.3-3.6, P = 0.003). The level of inflammatory cytokines in peripheral blood was higher in males during hospitalization. The renal (102/1588 6.5% vs. 63/1499 4.2%, in males and females, respectively, P = 0.002) and hepatic abnormality (650/1588 40.9% vs. 475/1499 31.7%, P = 0.003) were more common in male patients than in female patients. By analyzing dynamic changes of lymphocyte subsets after symptom onset, we found that the percentage of CD19+ B cells and CD4+ T cells was generally higher in female patients during the disease course of COVID-19. Notably, the protective RBD-specific IgG against SARS-CoV-2 sharply increased and reached a peak in the fourth week after symptom onset in female patients, while gradually increased and reached a peak in the seventh week after symptom onset in male patients. Males had an unfavorable prognosis, higher inflammation, a lower percentage of lymphocytes, and indolent antibody responses during SARS-CoV-2 infection and recovery. Early medical intervention and close monitoring are important, especially for male COVID-19 patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hyperandrogenism is a core factor in the series of reproductive and endocrine metabolic disorders involved in polycystic ovary syndrome (PCOS). Abnormalities in enzymatic activity and the expression ...of ovarian granular cell layer P450arom and theca cell P450c17α can lead to an atypical environment of local ovarian hormones, including excessive androgen levels. Rat models prepared with letrozole exhibit similar endocrine and histological changes to those that occur in human PCOS. We used such a model to study the role of electro-acupuncture (EA) in regulating ovarian P450arom and P450c17α enzymatic activity and mRNA expression in PCOS rats. Female Sprague Dawley (SD) rats aged 42 days were randomly divided into 3 groups (control, PCOS, and PCOS EA) consisting of 10 rats each. The PCOS and PCOS EA groups were administered a gavage of 1.0 mg/kg(-1) of letrozole solution once daily for 21 consecutive days. Beginning in the ninth week, the PCOS EA group was administered low-frequency EA treatment daily for 14 consecutive days. After the treatment, we obtained the following results. The estrous cycles were restored in 8 of the 10 rats in the PCOS EA group, and their ovarian morphologies and ultrastructures normalized. The peripheral blood measurements (with ELISA) showed significantly decreased androgens (i.e., androstenedione and testosterone) with significantly increased estrogens (i.e., estrone, estradiol) and increased P450arom with decreased P450C17α. Immunohistochemistry and Western blotting methods showed enhanced expression of ovarian granular cell layer P450arom as well as decreased expression of theca cell layer P450C17α. Fluorescence quantitative PCR methods showed enhanced expression of ovarian granular cell layer P450arom mRNA as well as decreased expression of theca cell layer P450C17α mRNA. These results may help explain the effects of electro-acupuncture in changing the local ovarian hyperandrogenic environment and improving reproductive and endocrine metabolic disorders in PCOS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Electroacupuncture restores the estrous cycle in 80% of PCOS rats and improves the ovarian morphology.•Electroacupuncture increases P450arom and estradiol levels, and decreases testosterone level in ...peripheral serum of rats.•Electroacupuncture increases FSHR expression and decreases AMH and AMHR II expressions in follicle granulosa cells of rats.•Electroacupuncture regulates imbalance of FSH and AMH in PCOS rats.
Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and follicular arrest. These two characteristics may result from an imbalance between anti-Müllerian hormone and follicle stimulating hormone. Electroacupuncture is effective in improving hyperandrogenism and follicular arrest in PCOS; however, the mechanism is not sufficiently clear. This study aimed to elucidate whether electroacupuncture in PCOS is exerted by regulating an imbalance of anti-Müllerian hormone and follicle stimulating hormone. In this study, a rat model of polycystic ovary syndrome was treated with low-frequency electroacupuncture at acupoints (CV-3 and CV-4). To observe the mechanism of electroacupuncture in PCOS, we first observed the estrous cycle. We then observed ovarian morphology by hematoxylin-eosin staining and evaluated levels of testosterone, estradiol, P450arom, follicle stimulating hormone and its receptor, and anti-Müllerian hormone and its receptor by enzyme-linked immunosorbent assay, western blotting, double immunofluorescence assay and real-time PCR. Our results showed that in 80% of rats in the electroacupuncture acupoints group, their estrous cycle recovered, ovarian morphology significantly improved, testosterone level significantly decreased, and levels of estradiol and P450arom significantly increased in peripheral serum after 14 consecutive days of treatment (P < 0.01). The expression of anti-Müllerian hormone and anti-Müllerian hormone type II receptor decreased (P < 0.05), whereas the expression of follicle stimulating hormone receptor increased (P < 0.05). These results indicated that electroacupuncture improved hyperandrogenism and follicular arrest by decreasing the excessive expression of AMH to regulate FSH and AMH imbalance in granulosa cells in PCOS.
The analysis of cancer diversity based on a logical framework of hallmarks has greatly improved our understanding of the occurrence, development and metastasis of various cancers.
We designed Cancer ...Hallmark Genes (CHG) database which focuses on integrating hallmark genes in a systematic, standard way and annotates the potential roles of the hallmark genes in cancer processes. Following the conceptual criteria description of hallmark function the keywords for each hallmark were manually selected from the literature. Candidate hallmark genes collected were derived from 301 pathways of KEGG database by Lucene and manually corrected.
Based on the variation data, we finally identified the hallmark genes of various types of cancer and constructed CHG. And we also analyzed the relationships among hallmarks and potential characteristics and relationships of hallmark genes based on the topological structures of their networks. We manually confirm the hallmark gene identified by CHG based on literature and database. We also predicted the prognosis of breast cancer, glioblastoma multiforme and kidney papillary cell carcinoma patients based on CHG data.
In summary, CHG, which was constructed based on a hallmark feature set, provides a new perspective for analyzing the diversity and development of cancers.
COVID-19 has resulted in high mortality worldwide. Information regarding cardiac markers for precise risk-stratification is limited. We aim to discover sensitive and reliable early-warning biomarkers ...for optimizing management and improving the prognosis of COVID-19 patients.
A total of 2954 consecutive COVID-19 patients who were receiving treatment from the Wuhan Huoshenshan Hospital in China from February 4 to April 10 were included in this retrospective cohort. Serum levels of cardiac markers were collected after admission. Coronary artery disease diagnosis and survival status were recorded. Single-cell RNA-sequencing and bulk RNA-sequencing from different cohorts of non-COVID-19 were performed to analyze SARS-CoV-2 receptor expression.
Among 2954 COVID-19 patients in the analysis, the median age was 60 years (50-68 years), 1461 (49.5%) were female, and 1515 (51.3%) were severe/critical. Compared to mild/moderate (1439, 48.7%) patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. In severe/critical COVID-19 patients, those with abnormal serum levels of BNP (42 24.6% vs 7 1.1%), hs-TNI (38 48.1% vs 6 1.0%), α- HBDH (55 10.4% vs 2 0.2%), CK-MB (45 36.3% vs 12 0.9%), and LDH (56 12.5% vs 1 0.1%) had a significantly higher mortality rate compared to patients with normal levels. The same trend was observed in the ICU admission rate. Severe/critical COVID-19 patients with pre-existing coronary artery disease (165/1,155 10.9%) had more cases of BNP (52 46.5% vs 119 16.5%), hs-TNI (24 26.7% vs 9.6 %, α- HBDH (86 55.5% vs 443 34.4%), CK-MB (27 17.4% vs 97 7.5%), and LDH (65 41.9% vs 382 29.7%), when compared with those without coronary artery disease. There was enhanced SARS-CoV-2 receptor expression in coronary artery disease compared with healthy controls. From regression analysis, patients with five elevated cardiac markers were at a higher risk of death (hazards ratio 3.4 95% CI 2.4-4.8).
COVID-19 patients with pre-existing coronary artery disease represented a higher abnormal percentage of cardiac markers, accompanied by high mortality and ICU admission rate. BNP together with hs-TNI, α- HBDH, CK-MB and LDH act as a prognostic biomarker in COVID-19 patients with or without pre-existing coronary artery disease.
Methamphetamine use disorder (MAUD) and gambling disorder (GD) frequently co-occur. Individuals with both conditions are typically more difficult to treat than those with either disorder alone. This ...study aimed to investigate the co-occurrence and clinical characteristics of people with MAUD and GD. Between March 2018 and August 2020, 350 men with methamphetamine use entering a compulsory drug rehabilitation center in Changsha, Hunan Province received semi-structured interviews. Participants completed the Barratt Impulsiveness Scale-11 and provided information on childhood upbringings and drug use characteristics. Independent sample
t
-tests compared differences between individuals with MAUD and with and without co-occurring GD. Dichotomous logistic regression was used to statistically predict co-occurring GD. The prevalence of GD was 45.1%. Most individuals (39.1% overall) had post-onset methamphetamine use (PoMAU-GD). The number of MAUD symptoms, history of gambling by family members, age of first sexual activity, and non-planning impulsivity statistically predicted PoMAU-GD, jointly explaining 24.0% of the total variance. The regression model fit well (HLχ
2
= 5.503,
p
= 0.70), in which the specificity was 0.80, the sensitivity was 0.64, and the area under the curve was 0.79 (95%CI: 0.75–0.84). This study clarifies the prevalence of and potential risk factors for GD among individuals engaging in compulsory MAUD treatment in China. The high prevalence and associated clinical features of GD in the MAUD group highlight the importance of screening for GD in this population and intervening accordingly.
Abstract
Male breast cancer (MBC) is a rare but aggressive malignancy with cellular and immunological characteristics that remain unclear. Here, we perform transcriptomic analysis for 111,038 single ...cells from tumor tissues of six MBC and thirteen female breast cancer (FBC) patients. We find that that MBC has significantly lower infiltration of T cells relative to FBC. Metastasis-related programs are more active in cancer cells from MBC. The activated fatty acid metabolism involved with
FASN
is related to cancer cell metastasis and low immune infiltration of MBC. T cells in MBC show activation of p38 MAPK and lipid oxidation pathways, indicating a dysfunctional state. In contrast, T cells in FBC exhibit higher expression of cytotoxic markers and immune activation pathways mediated by immune-modulatory cytokines. Moreover, we identify the inhibitory interactions between cancer cells and T cells in MBC. Our study provides important information for understanding the tumor immunology and metabolism of MBC.
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