Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans.

Human infertility is a multifactorial disease that affects 8%-12% of reproductive-aged couples worldwide. However, the genetic causes of human infertility are still poorly understood. Synaptonemal complex (SC) is a conserved tripartite structure that holds homologous chromosomes together and plays an indispensable role in the meiotic progression. Here, we identified three homozygous mutations in the SC coding gene C14orf39/SIX6OS1 in infertile individuals from different ethnic populations by whole-exome sequencing (WES). These mutations include a frameshift mutation (c.204_205del [p.His68Glnfs∗2]) from a consanguineous Pakistani family with two males suffering from non-obstructive azoospermia (NOA) and one female diagnosed with premature ovarian insufficiency (POI) as well as a nonsense mutation (c.958G>T [p.Glu320∗]) and a splicing mutation (c.1180-3C>G) in two unrelated Chinese men (individual P3907 and individual P6032, respectively) with meiotic arrest. Mutations in C14orf39 resulted in truncated proteins that retained SYCE1 binding but exhibited impaired polycomplex formation between C14ORF39 and SYCE1. Further cytological analyses of meiosis in germ cells revealed that the affected familial males with the C14orf39 frameshift mutation displayed complete asynapsis between homologous chromosomes, while the affected Chinese men carrying the nonsense or splicing mutation showed incomplete synapsis. The phenotypes of NOA and POI in affected individuals were well recapitulated by Six6os1 mutant mice carrying an analogous mutation. Collectively, our findings in humans and mice highlight the conserved role of C14ORF39/SIX6OS1 in SC assembly and indicate that the homozygous mutations in C14orf39/SIX6OS1 described here are responsible for infertility of these affected individuals, thus expanding our understanding of the genetic basis of human infertility.

The influence of integrated healthcare on the nursing effect, negative emotions, and heart failure indicators in acute heart failure patients.

OBJECTIVE: To investigate the effect of integrated healthcare on the nursing of heart failure patients, as well as its influence on the negative emotions and the factors related to heart failure. METHODS: 150 patients with acute heart failure admitted to our hospital were randomly divided into two groups. The patients in the control group underwent routine care, and the patients in the research group were treated with integrated healthcare. The two groups' general information, symptom improvements, six-minute walking distances, emotional conditions, quality of life (MLHFQ scores), N-terminal brain natriuretic peptide (NT-proBNP) levels, mortality rates, rehospitalization rates, and satisfaction rates were compared. RESULTS: The time required for symptom improvement in the research group was shorter than it was in the control group (P<0.001). The patients' six-minute walking distances in the research group were longer than the distances in the control group (P<0.001). There were no differences in the emotional changes between the two groups before the nursing (P>0.05), but after the nursing, the negative emotion scores in the research group were significantly decreased when compared with the control group (P<0.001). The MLHFQ scores and the NT-proBNP levels in the research group were both lower than they were in the control group (P<0.001). No significant differences were observed between the two groups in their mortality or rehospitalization rates (P>0.05). However, the patient satisfaction rates in the research group was higher than they were in the control group (P<0.05). CONCLUSION: As a care plan for patients with acute heart failure, the integrated healthcare plan significantly relieved the patients' anxiety and efficiently improved the patients' quality of life, an indication that integrated healthcare is worth promoting and applying clinically.

The Effect of Group Random Quality Control on the First Aid Ability of Ward Doctors and Nurses with Respect to the Resuscitation of Patients with In-Hospital Cardiac Arrest.

OBJECTIVE: This study was designed to verify the effect of group random quality control on the first aid ability of ward doctors and nurses with regard to the resuscitation of patients with in-hospital cardiac arrest (IHCA). METHODS: The first aid quality control team of our hospital was established in December 2018, when the number, qualifications, organizational structure, quality control methods, and responsibilities of the team and team members were determined. The baseline data and assessment results of examinees, the rates of return of spontaneous circulation (ROSC), and the discharge survival rate of IHCA patients in 2019 and 2020 were compared. RESULTS: There were no significant differences in the baseline data of examinees at each stage (p > 0.05). As time went on, the results of the four practical examinations were significantly improved (pairwise comparison, p < 0.05). The number of problems in examinations was significantly higher for physicians than for nurses. After guidance in department relearning, the incidence of related problems was significantly reduced, but the mastery of the frequency and depth of extracorporeal cardiac compression were not always up to standard. The proportion of critically ill patients and the incidence of IHCA in the hospital in 2020 was higher than in 2019 (p < 0.05), and the ROSC rate was also significantly higher than it was in 2019 (p < 0.05), but the difference in the survival rate at discharge was not statistically significant (p > 0.05). CONCLUSION: Group random quality control meets the needs of IHCA emergencies, and it can improve the first aid skills and organizational coordination of doctors and nurses on the ward through continuous discovery and problem solving so that the ultimate goal of improving the success rate of resuscitation can be achieved.

Effect and prognosis of emergency nursing path in patients with acute stroke.

OBJECTIVE: To evaluate the effect and prognosis of the emergency nursing path in patients with acute stroke. METHODS: In this prospective study, 108 patients with acute stroke were randomly divided into an observation group (n=54, implementing the emergency nursing path) and a control group (n=54, implementing emergency routine care). We compared the rescue time-related indicators, neurological function, cognitive function and prognosis of the two groups. RESULTS: The time from admission to diagnosis and the time from diagnosis to specialist treatment in the observation group were shorter than those in the control group (all P<0.05). After two weeks of intervention, the score of National Institute of Health Stroke Scale in the two groups of patients were lower than before the intervention, and the observation group was even lower (all P<0.05). After one month of discharge, the score of Activity of Daily Living Scale decreased while the scores of Montreal Cognitive Assessment, Mini-mental State Examination and Glasgow Outcome Scale increased in both groups, with more significant changes in the observation group (all P<0.05). The disability rate in the observation group was lower than that in the control group (P<0.05). CONCLUSION: The implementation of emergency nursing could significantly shorten the time from admission to specialist treatment for patients with acute stroke. It could also promote the recovery of neurological and cognitive functions, which was conducive to the prognosis of patients.

NUDT21 negatively regulates PSMB2 and CXXC5 by alternative polyadenylation and contributes to hepatocellular carcinoma suppression.

Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism and involved in many diseases, including cancer. CFIm25, a subunit of the cleavage factor I encoded by NUDT21, is required for 3'RNA cleavage and polyadenylation. Although it has been recently reported to be involved in glioblastoma tumor suppression, its roles and the underlying functional mechanism remain unclear in other types of cancer. In this study, we characterized NUDT21 in hepatocellular carcinoma (HCC). Reduced expression of NUDT21 was observed in HCC tissue compared to adjacent non-tumorous compartment. HCC patients with lower NUDT21 expression have shorter overall and disease-free survival times than those with higher NUDT21 expression after surgery. Knockdown of NUDT21 promotes HCC cell proliferation, metastasis, and tumorigenesis, whereas forced expression of NUDT21 exhibits the opposite effects. We then performed global APA site profiling analysis in HCC cells and identified considerable number of genes with shortened 3'UTRs upon the modulation of NUDT21 expression. In particular, we further characterized the NUDT21-regulated genes PSMB2 and CXXC5. We found NUDT21 knockdown increases usage of the proximal polyadenylation site in the PSMB2 and CXXC5 3' UTRs, resulting in marked increase in the expression of PSMB2 and CXXC5. Moreover, knockdown of PSMB2 or CXXC5 suppresses HCC cell proliferation and invasion. Taken together, our study demonstrated that NUDT21 inhibits HCC proliferation, metastasis and tumorigenesis, at least in part, by suppressing PSMB2 and CXXC5, and thereby provided a new insight into understanding the connection of HCC suppression and APA machinery.

Prognostic role of microRNAs in human gastrointestinal cancer: A systematic review and meta-analysis.

BACKGROUND: Gastrointestinal cancers (GICs) mainly including esophageal, gastric and colorectal cancer, are the most common cause of cancer-related death and lead into high mortality worldwide. We performed this systematic review and meta-analysis to elucidate relationship between multiple microRNAs (miRs) expression and survival of GIC patients. METHODS: We searched a wide range of database. Fixed-effects and random-effects models were used to calculate the pooled hazard ratio values of overall survival and disease free survival. In addition, funnel plots were used to qualitatively analyze the publication bias and verified by Begg's test while it seems asymmetry. RESULTS: 60 studies involving a total of 6225 patients (1271 with esophageal cancer, 3467 with gastric cancer and 1517 with colorectal cancer) were included in our meta-analysis. The pooled hazard ratio values of overall survival related to different miRs expression in esophageal, gastric, colorectal and gastrointestinal cancer were 2.10 (1.78-2.49), 2.02 (1.83-2.23), 2.54 (2.14-3.02) and 2.15 (1.99-2.31), respectively. We have identified a total of 59 miRs including 23 significantly up-regulated expression miRs (miR-214, miR-17, miR-20a, miR-200c, miR-107, miR-27a, etc.) and 36 significantly down-regulated expression miRs (miR-433, let-7g, miR-125a-5p, miR-760, miR-206, miR-26a, miR-200b, miR-185, etc.) correlated with poor prognosis in GIC patients. Moreover, 35 of them revealed mechanisms. CONCLUSION: Overall, specific miRs are significantly associated with the prognosis of GIC patients and potentially eligible for the prediction of patients survival. It also provides a potential value for clinical decision-making development and may serve as a promising miR-based target therapy waiting for further elucidation.