Machine learning and integrative analysis identify the common pathogenesis of azoospermia complicated with COVID-19.

Background: Although more recent evidence has indicated COVID-19 is prone to azoospermia, the common molecular mechanism of its occurrence remains to be elucidated. The aim of the present study is to further investigate the mechanism of this complication. Methods: To discover the common differentially expressed genes (DEGs) and pathways of azoospermia and COVID-19, integrated weighted co-expression network (WGCNA), multiple machine learning analyses, and single-cell RNA-sequencing (scRNA-seq) were performed. Results: Therefore, we screened two key network modules in the obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) samples. The differentially expressed genes were mainly related to the immune system and infectious virus diseases. We then used multiple machine learning methods to detect biomarkers that differentiated OA from NOA. Enrichment analysis showed that azoospermia patients and COVID-19 patients shared a common IL-17 signaling pathway. In addition, GLO1, GPR135, DYNLL2, and EPB41L3 were identified as significant hub genes in these two diseases. Screening of two different molecular subtypes revealed that azoospermia-related genes were associated with clinicopathological characteristics of age, hospital-free-days, ventilator-free-days, charlson score, and d-dimer of patients with COVID-19 (P < 0.05). Finally, we used the Xsum method to predict potential drugs and single-cell sequencing data to further characterize whether azoospermia-related genes could validate the biological patterns of impaired spermatogenesis in cryptozoospermia patients. Conclusion: Our study performs a comprehensive and integrated bioinformatics analysis of azoospermia and COVID-19. These hub genes and common pathways may provide new insights for further mechanism research.

Relationships among inferiority feelings, fear of negative evaluation, and social anxiety in Chinese junior high school students.

Introduction: This study aimed to explore the relationship between feelings of inferiority and social anxiety in Chinese junior high school students. In addition, it examined the potential mediating effect of fear of negative evaluation in this relationship. Methods: A survey was administered to a sample of 734 Chinese junior high school students. The Feelings of Inadequacy Scale, Brief Fear of Negative Evaluation Scale, and Social Avoidance Distress Scale were used. Results: First, there were significant positive correlations between all subscales for the inferiority feelings, social anxiety, and fear of negative evaluation. Furthermore, fear of negative evaluation mediated the predictive effects of four inferiority subscales (i.e., self-esteem, academic ability, appearance, and physical ability) for social anxiety. However, the total score for the sense of inferiority and social confidence subscale lacked this mediating effect. Conclusion: The inferiority feelings of self-esteem, academic ability, appearance, and physical ability may directly and indirectly predict social anxiety through fear of negative evaluation.

GPRC5D CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma (POLARIS): a first-in-human, single-centre, single-arm, phase 1 trial.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) has shown activity in treating relapsed or refractory multiple myeloma; however, relapse is still common, and new targets are needed. We aimed to assess the activity and safety profile of G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma. METHODS: POLARIS was a first-in-human, single-centre, single-arm, phase 1 trial of GPRC5D-targeted CAR T cells (OriCAR-017) done at the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. Eligible patients were adults aged 18-75 years with a diagnosis of relapsed or refractory multiple myeloma and an ECOG performance status of 0-2, had GPRC5D expression in bone marrow plasma cells greater than 20% or were positive for GPRC5D by immunohistochemistry, and had received at least three previous lines of treatment including proteasome inhibitors, immunomodulatory drugs, and chemotherapy. Patients were consecutively assigned to receive a single dose of intravenous OriCAR-017 at 1 × 106 CAR T cells per kg, 3 × 106 CAR T cells per kg, or 6 × 106 CAR T cells per kg in the dose-escalation phase. In the expansion phase, patients received the recommended phase 2 dose. Recruitment to the expansion phase terminated early due to the COVID-19 pandemic on May 1, 2022. The primary endpoints were safety, the maximum tolerated dose and the recommended phase 2 dose. Safety and activity analyses included all patients who received OriCAR-017. This trial is registered with ClinicalTrials.gov, NCT05016778. This trial has been completed and is entering long-term follow-up. FINDINGS: Between June 9, 2021, and Feb 28, 2022, we recruited 13 patients for inclusion into the study. One patient was excluded because of GPRC5D negativity and two patients discontinued after apheresis because of rapid progression. Nine patients were assigned to the dose escalation phase (three received 1 × 106 CAR T cells per kg, three received 3 × 106 CAR T cells per kg, and three received 6 × 106 CAR T cells per kg). The maximum tolerated dose was not identified, because no dose-limiting toxic effects were observed. On the basis of safety and preliminary activity, the recommended phase 2 dose was set at 3 × 106 CAR T cells per kg, which was received by one additional patient in the dose expansion phase. Five patients (50%) were female, five (50%) were male, and all were Chinese. Five patients (50%) were previously treated with BCMA-targeted CAR T-cell therapy. Median follow-up was 238 days (IQR 182-307). There were no serious adverse events and no treatment-related deaths. The most common grade 3 or worse adverse events were haematological, including neutropenia (ten [100%] of ten patients), thrombocytopenia (nine [90%]), leukopenia (nine [90%]), and anaemia (seven [70%]). All patients had cytokine release syndrome (nine [90%] grade 1 and one [10%] grade 2). No neurological toxic effects were reported. Ten (100%) of ten patients had an overall response, of whom six (60%) had a stringent complete response and four (40%) had very good partial response. Two patients discontinued due to disease progression (one GPRC5D-positive patient in the middle-dose group and one GPRC5D-negative patient in the low-dose group). INTERPRETATION: The results of this study suggest that GPRC5D is an active target for immunotherapy in multiple myeloma. GPRC5D-targeted CAR T-cell therapy is a promising treatment modality for patients with relapsed or refractory multiple myeloma and deserves further testing. FUNDING: OriCell Therapeutics.

Comparison of lung image quality between CT Ark and Brilliance 64 CT during COVID-19.

AIM: This study is to compare the lung image quality between shelter hospital CT (CT Ark) and ordinary CT scans (Brilliance 64) scans. METHODS: The patients who received scans with CT Ark or Brilliance 64 CT were enrolled. Their lung images were divided into two groups according to the scanner. The objective evaluation methods of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were used. The subjective evaluation methods including the evaluation of the fine structure under the lung window and the evaluation of the general structure under the mediastinum window were compared. Kappa method was used to assess the reliability of the subjective evaluation. The subjective evaluation results were analyzed using the Wilcoxon rank sum test. SNR and CNR were tested using independent sample t tests. RESULTS: There was no statistical difference in somatotype of enrolled subjects. The Kappa value between the two observers was between 0.68 and 0.81, indicating good consistency. For subjective evaluation results, the rank sum test P value of fine structure evaluation and general structure evaluation by the two observers was ≥ 0.05. For objective evaluation results, SNR and CNR between the two CT scanners were significantly different (P<0.05). Notably, the absolute values ​​of SNR and CNR of the CT Ark were larger than Brilliance 64 CT scanner. CONCLUSION: CT Ark is fully capable of scanning the lungs of the COVID-19 patients during the epidemic in the shelter hospital.

Advances in research on SARS-CoV-2

An unexplained pneumonia outbreak at the end of 2019 was found to be associated with a novel coronavirus (SARS-CoV-2). The virus is the seventh known coronavirus that can infect humans. In a short period of time, this coronavirus infection has spread to many regions of the world, causing the concern of countries around the world. At present, related research on SARS-CoV-2 is still in its infancy. This article summarizes the findings of the latest research related to SARS-CoV-2 to provide reference for subsequent research and prevention.