HELQ deficiency impairs the induction of primordial germ cell-like cells.

Helicase POLQ-like (HELQ) is a DNA helicase essential for the maintenance of genome stability. A recent study identified two HELQ missense mutations in some cases of infertile men. However, the functions of HELQ in the process of germline specification are not well known and whether its function is conserved between mouse and human remains unclear. Here, we revealed that Helq knockout (Helq-/-) could significantly reduce the efficiency of mouse primordial germ cell-like cell (PGCLC) induction. In addition, Helq-/- embryonic bodies exhibited a severe apoptotic phenotype on day 6 of mouse PGCLC induction. p53 inhibitor treatment could partially rescue the generation of mouse PGCLCs from Helq mutant mouse embryonic stem cells. Finally, the genetic ablation of HELQ could also significantly impede the induction of human PGCLCs. Collectively, our study sheds light on the involvement of HELQ in the induction of both mouse and human PGCLCs, providing new insights into the mechanisms underlying germline differentiation and the genetic studies of human fertility.

Current Controversy and Developments Regarding the Cytoreductive Prostatectomy for Oligometastatic Prostate Cancer.

Oligometastatic prostate cancer is a term that is most often used to refer to limited sites of disseminated tumor growth following primary radical prostatectomy (RP) or radiotherapy (RT), while de novo oligometastatic is a term that is used to refer to prostate tumors that have disseminated to limited sites before definitive treatment. In patients with de novo oligometastatic prostate cancer, treatment planning must thus consider the need to manage the primary tumor and the associated distant lesions. Traditionally, resectioning primary metastatic tumors is not thought to offer significant benefits to affected patients while increasing their risk of surgery-related complications. Recent clinical evidence indicates that patients undergoing cytoreductive prostatectomy (CRP) may observe substantial enhancements in overall survival rates while not experiencing a noticeable decline in their quality of life. Nevertheless, based on the current body of evidence, it is deemed inadequate to justify revising clinical guidelines. Consequently, it is not advisable to propose CRP for patients with oligometastatic prostate cancer. The present review was compiled to summarize available data regarding the indications, functional outcomes, and oncological outcomes associated with cytoreductive radical prostatectomy to provide a robust and objective foundation that can be used to better assess the value of this interventional strategy from a clinical perspective.

Clinical characteristics and host immunity responses of SARS-CoV-2 Omicron variant BA.2 with deletion of ORF7a, ORF7b and ORF8.

BACKGROUND: The pathogenicity and virulence of the Omicron strain have weakened significantly pathogenesis of Omicron variants. Accumulating data indicated accessory proteins play crucial roles in host immune evasion and virus pathogenesis of SARS-CoV-2. Therefore, the impact of simultaneous deletion of accessory protein ORF7a, ORF7b and ORF8 on the clinical characteristics and specific immunity in Omicron breakthrough infected patients (BIPs) need to be verified. METHODS: Herein, plasma cytokines were identified using a commercial Multi-cytokine detection kit. Enzyme-linked immunosorbent assay and pseudovirus neutralization assays were utilized to determine the titers of SARS-CoV-2 specific binding antibodies and neutralizing antibodies, respectively. In addition, an enzyme-linked immunospot assay was used to quantify SARS-CoV-2 specific T cells and memory B cells. RESULTS: A local COVID-19 outbreak was caused by the Omicron BA.2 variant, which featured a deletion of 871 base pairs (∆871 BA.2), resulting in the removal of ORF7a, ORF7b, and ORF8. We found that hospitalized patients with ∆871 BA.2 had significantly shorter hospital stays than those with wild-type (WT) BA.2. Plasma cytokine levels in both ∆871 BA.2 and WT BA.2 patients were within the normal range of reference, and there was no notable difference in the titers of SARS-CoV-2 ancestor or Omicron-specific binding IgG antibodies, neutralizing antibody titers, effector T cells, and memory B cells frequencies between ∆871 BA.2 and WT BA.2 infected adult patients. However, antibody titers in ∆871 BA.2 infected adolescents were higher than in adults. CONCLUSIONS: The simultaneous deletion of ORF7a, ORF7b, and ORF8 facilitates the rapid clearance of the BA.2 variant, without impacting cytokine levels or affecting SARS-CoV-2 specific humoral and cellular immunity in Omicron-infected individuals.

Dynamic changes in PSA levels predict prognostic outcomes in prostate cancer patients undergoing androgen -deprivation therapy: A multicenter retrospective analysis.

Background: Androgen-deprivation therapy (ADT) is used for the treatment of prostate cancer. However, the specific risk factors for the development of castration-resistant disease are still unclear. The present study sought to identify predictors of patient prognostic outcomes through analyses of clinical findings in large numbers of prostate cancer patients following ADT treatment. Methods: Data pertaining to 163 prostate cancer patients treated at the Second Affiliated Hospital of Bengbu Medical University and Maoming People's Hospital from January 1, 2015, to December 30, 2020, were retrospectively analyzed. Dynamic changes in prostate-specific antigen (PSA) levels were regularly assessed, including both time to nadir (TTN) and nadir PSA (nPSA). Univariate and multivariate analyses were performed with Cox risk proportional regression models, while differences in biochemical progression-free survival (bPFS) were compared among groups with Kaplan-Meier curves and log-rank tests. Results: The bPFS values over the median 43.5-month follow-up period differed significantly between patients with nPSA levels < 0.2 ng/mL and ≥ 0.2 ng/mL, being 27.6 months and 13.5 months, respectively (log-rank P < 0.001). A significant difference in median bPFS was also observed when comparing patients with a TTN ≥ 9 months (27.8 months) to those with a TTN < 9 months (13.5 months) (log-rank P < 0.001). Conclusions: TTN and nPSA are valuable predictors of prognosis in prostate cancer patients after ADT treatment, with better outcomes evident in patients with nPSA < 0.2 ng/mL and TTN > 9 months.

Giant adrenal ganglioneuroma in children: a case report.

BACKGROUND: Ganglioneuromas (GNs) arise from the Schwann cells, ganglion cells, and neuronal tissues, and are extremely rare, slow-growing, benign tumors. GN has usually grown very large when it is diagnosed since no specific clinical symptoms or laboratory findings indicating GN are available, especially when it occurs in the retroperitoneal space. Total resection of the tumor is the recommended treatment. We present the imaging and pathological findings of a giant adrenal GN in a child. A 7-year-old boy suffered from nausea and postprandial vomiting for 1 week with no precipitating factors. There was no family history of any disease, and the boy did not suffer from any disease in the past. Biochemical examination showed normal results. Physical examination showed an immobilized palpable mass in the left abdominal area. Abdominal computed tomography revealed a 13 cm × 10 cm solid mass in the retroperitoneal space. The mass showed slight and heterogeneous enhancement after injection of a contrasting agent. The mass was surgically resected locally to address the embedded abdominal vessels, and the histopathological and immunohistochemical diagnosis of the mass was GN. After the surgery, the symptoms of nausea and vomiting were relieved, and no complications occurred. CONCLUSION: GN should be considered when a child presents with a giant retroperitoneal hypodense mass and the mass presents uneven and delayed enhancement. Histopathology is the golden standard for the diagnosis of GN. Currently, surgical excision is the optimal treatment.

Urinary proteome analysis of acute kidney injury in post-cardiac surgery patients using enrichment materials with high-resolution mass spectrometry.

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) may increase the mortality and incidence rates of chronic kidney disease in critically ill patients. This study aimed to investigate the underlying correlations between urinary proteomic changes and CSA-AKI. Methods: Nontargeted proteomics was performed using nano liquid chromatography coupled with Orbitrap Exploris mass spectrometry (MS) on urinary samples preoperatively and postoperatively collected from patients with CSA-AKI. Gemini C18 silica microspheres were used to separate and enrich trypsin-hydrolysed peptides under basic mobile phase conditions. Differential analysis was conducted to screen out urinary differential expressed proteins (DEPs) among patients with CSA-AKI for bioinformatics. Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis was adopted to identify the altered signal pathways associated with CSA-AKI. Results: Approximately 2000 urinary proteins were identified and quantified through data-independent acquisition MS, and 324 DEPs associated with AKI were screened by univariate statistics. According to KEGG enrichment analysis, the signal pathway of protein processing in the endoplasmic reticulum was enriched as the most up-regulated DEPs, and cell adhesion molecules were enriched as the most down-regulated DEPs. In protein-protein interaction analysis, the three hub targets in the up-regulated DEPs were α-1-antitrypsin, ß-2-microglobulin and angiotensinogen, and the three key down-regulated DEPs were growth arrest-specific protein 6, matrix metalloproteinase-9 and urokinase-type plasminogen activator. Conclusion: Urinary protein disorder was observed in CSA-AKI due to ischaemia and reperfusion. The application of Gemini C18 silica microspheres can improve the protein identification rate to obtain highly valuable resources for the urinary DEPs of AKI. This work provides valuable knowledge about urinary proteome biomarkers and essential resources for further research on AKI.

Impact of 60 days of 6° head down bed rest on cardiopulmonary function, and the effects of Taikong Yangxin Prescription as a countermeasure.

OBJECTIVE: To study the changes in cardiopulmonary function induced by mid/long-term simulated microgravity with 6° head down bed rest (HDBR), and the effects of Taikong Yangxin Prescription (, TYP) as a countermeasure. METHODS: Fourteen healthy male volunteers were randomly divided into a control group and a Chinese medicine (CM) group (7 in each group) by a random digital table based on their body weight. Both groups underwent 6° HDBR for 60 days. Subjects in the CM group received daily TYP pills and subjects in the control group received daily placebo pills. Cardiac systolic and pumping functions were measured by echocardiography before HDBR; on days 20, 42, and 57 of HDBR; and on day 3 of recovery after HDBR (R+3). Cardiopulmonary functional reserve and exercise capacity were evaluated before HDBR, on day 29, and on day R+3 by exercise testing. RESULTS: The heart rate (HR) increased gradually during HDBR. The HR was significantly higher on day 57 than before HDBR in the control group (P<0.05), but did not increase significantly in the CM group. The stroke volume/stroke volume index, ejection fraction, and left ventricular fractional shortening tended to decrease over time in the control group, but not in the CM group. These parameters were significantly higher in the CM group than in the control group on day 42 (P<0.05 or <0.01). Exercise testing showed that maximum O2 consumption (VO2max), metabolic equivalents, relative O2 consumption (VO2), O2 pulse, and exercise duration were significantly lower on day 29 than before HDBR in the control group, but not in the CM group. CONCLUSIONS: Sixty days of 6° HDBR induced a reduction in cardiac systolic and pumping functions, and reduced cardiopulmonary functional reserve and exercise capacity. Administration of TYP significantly improved cardiac systolic and pumping functions, and maintained cardiopulmonary functional reserve and exercise capacity.

[Effects of body position changes on frequency domain correlative cardiogram in pilots].

OBJECTIVE: To study the effects of the body position changes on FCG in pilots so as to explore the possibility of using FCG as an indicator of medical monitoring and medical support. METHOD: 65 pilots were examined in 4 different body positions, i.e. supine position, head-down position, standing position and sitting position. Twelve channel routine electrocardiogram was recorded synchronously, and their complaints were also recorded. RESULT: The grade distribution and abnormal cases of the FCG varied with the body positions. The orders of changing magnitude were: the standing position, the head-down position, the sitting position and the supine position. The changes accorded with that of 12 channels routine ECG synchronously recorded and complaints of the subjects. CONCLUSION: The FCG was an objective index representing the cardiac functional status.

[Effects of 7 d head-down bed rest on human vectorcardiogram (VCG)].

OBJECTIVE: To study the effects of short-term simulated weightlessness on human vectorcardiogram (VCG). METHOD: Seven d -6 degrees head-down bed rest (HDBR) was used to simulate weightlessness. Eight healthy males, aged 19-21, served as the subjects. VCG was recorded before and on day 1, 3, 7 of HDBR. RESULT: QRS loop in the horizontal plane rotated counterclockwise, while QRS loop in the right sagittal plane rotated clockwise during HDBR (P<0.05 or P<0.01). QRS-T angle in the horizontal and right sagittal plane increased significantly during HDBR. CONCLUSION: Seven d HDBR leads to changes of VCG parameters, which were all in normal ranges and in accordance with the volume changes of atrium and ventricle, but obviously different from those resulted from pathological ventricular thickening and myocardial ischemia.