Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

: Bacteroides, as one of the most abundant and diverse genera in the human gut, is regarded as a window into the study of gut microbiota-host interactions. Currently, CRISPR/Cas-based gene editing systems targeting Bacteroides have been widely applied, while the large size of Cas nucleases limits their potential application scenarios (such as in situ gut Bacteroides editing based on phage delivery). Therefore, this study aims to develop a compact and highly efficient genetic editing tool in Bacteroides., We developed a miniaturized CRISPR/Cas gene editing system for human gut Bacteroides. First, the editing capabilities of different miniaturized CRISPR/Cas systems, including AsCas12f, CasΦ2, and ISDge10, were evaluated in Bacteroides fragilis. Subsequently, the editing capability of AsCas12f was assessed across various Bacteroides species, and the size of this system was further optimized. The results demonstrated that the CRISPR/AsCas12f genome editing system exhibited the highest editing efficiency in B. fragilis. The CRISPR/AsCas12f system achieved efficient genome editing in B. fragilis, Bacteroides thetaiotaomicron, and Phocaeicola vulgatus. Furthermore, with a repair template of 500 bp homologous arms, the editing efficiency remained as high as 94.7%. In conclusion, CRISPR/AsCas12f can serve as a chassis tool enzyme for the development of Bacteroides-based miniature gene editors and derivative technologies, laying a foundation for the further development of gene editing technology for Bacteroides.
CRISPR-Cas Systems/genetics* ; Gene Editing/methods* ; Bacteroides/genetics* ; Humans ; Gastrointestinal Microbiome/genetics* ; Bacteroides fragilis/genetics*

Objective:To evaluate the item properties and applicability of the eHealth Literacy Scale in Web 3.0 context (eHLS-Web 3.0) among diabetic patients by applying classical test theory (CTT) and item response theory (IRT) to provide a new effective tool for assessing the level of eHealth literacy among diabetic patients.Methods:A cross-sectional study design was adopted and 230 diabetic patients from the inpatient endocrinology department of the Affiliated Yantai Yuhuangding Hospital of Qingdao University were selected by convenience sampling from November 2022 to May 2023 and were surveyed by using the self-general information questionnaire and eHLS-Web 3.0. The correlation coefficient method, Cronbach α coefficient, Guttman split-half reliability coefficient, and structural validity in CCT were used, and discriminant validity, convergent validity, and Samejima Graded Response model in IRT were used to evaluate the scale items. Results:The CTT results showed that Cronbach α coefficient for the eHLS-Web 3.0 was 0.973, the Guttman split-half reliability coefficient was 0.894, and the correlation coefficient between the items and the total score of the scale ranged from 0.708 to 0.845 (all P<0.01). Exploratory factor analysis extracted three common factors with a cumulative variance contribution rate of 76.75%, and the confirmatory factor analysis model had a good fit. The reliability of each dimension combination was >0.60, and the average variance extracted was >0.50. The square root of the average variance extracted from each dimension (0.817, 0.875, 0.845) was greater than the correlation coefficient between this dimension and other dimensions (0.742, 0.763, 0.715). The IRT results showed that the discrimination parameter of all the items ranged from 2.174 to 4.054, the difficulty coefficients increased with the increase of the level (- 2.471 - 2.187), and the average information content of all the items ranged from 1.217 to 2.609. Conclusions:The eHLS-Web 3.0 has good characteristics among diabetic patients as tested by CTT and IRT, and can be used as an effective tool to assess the eHealth literacy level of diabetic patients in China.

Objective To discuss the perioperative care and wound protection of xenotransplantation from genetically edited pigs to monkeys, with the goal of improving the success rate of such experimental procedures. Methods From October 2022 to October 2023, perioperative care and wound protection were performed on 7 recipient rhesus monkeys undergoing xenotransplantation of genetically edited pig tissues and organs. Customized wound protective garments were designed based on monkeys' size and surgical area to protect the wounds, alongside meticulous perioperative care. This included preoperative preparation and medication, intraoperative monitoring of physiological indicators and anesthesia management, and postoperative care comprising wound protection, observation and monitoring, and nutritional support. Results All seven monkeys successfully underwent xenotransplantation. With the aid of protective garments and detailed care, all surgical wounds healed by first intention, and postoperative recovery was satisfactory. Conclusion Proper care and wound protection during xenotransplantation from genetically edited pigs to monkeys not only promote wound healing, but also alleviate pain and harm to animals. This has significant implications for advancing experimental research in pig-monkey xenotransplantation and enhancing animal welfare.

Polyploid cells, which contain more than one set of chromosome pairs, are very common in nature. Polyploidy can provide cells with several potential benefits over their diploid counterparts, including an increase in cell size, contributing to organ growth and tissue homeostasis, and improving cellular robustness via increased tolerance to genomic stress and apoptotic signals. Here, we focus on why polyploidy in the cell occurs and which stress responses and molecular signals trigger cells to become polyploid. Moreover, we discuss its crucial roles in cell growth and tissue regeneration in the heart, liver, and other tissues.
Humans ; Liver ; Hepatocytes ; Cell Cycle ; Polyploidy ; Homeostasis

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.
Amyloidogenic Proteins/metabolism* ; Amyotrophic Lateral Sclerosis/genetics* ; Animals ; COVID-19 ; Cytoplasmic Granules/metabolism* ; Mammals ; SARS-CoV-2 ; Stress Granules

Objective:To explore the effect of intervention plan based on a shared decision-making model on the diabetes knowledge, self-efficacy, self-management behavior, and blood glucose level of patients with diabetic ketosis.Methods:From November 2019 to March 2020, a total of 212 patients with diabetic ketosis who were admitted to the Endocrinology Department of a ClassⅢGrade A hospital in Yantai were recruited by convenience sampling. Among them, 104 patients admitted from July to October 2019 were involved into the control group, and 108 patients for the experimental group. The control group was given regular health education, and the experimental group was given the education based on the shared decision-making model. The changes of diabetes knowledge, diabetes management self-efficacy, self-management behavior, fasting blood glucose (FBG) , 2-hour postprandial blood glucose (2hPG) , glycosylated hemoglobin value (HbA1c) in two groups were compared before intervention, 3 months and 6 months after intervention.Results:3 months and 6 months after the intervention, the scores of diabetes knowledge with 85 (89.3, 70.0) and 88 (71.3, 92) , diabetes self-efficacy with 77.5 (70.0, 88.0) and 79.2 (63.8, 92.4) , self-management behavior with [64.5 (55.8, 74.8) ] and [62.5 (53.9, 74.2) ]in the experimental group were significantly higher than those of the control group ( P<0.05) . The level of FBG, 2hPG, and HbA1c of the experimental group were lower than those of the control group, and the differences were statistically significant ( P<0.05) . There was no significant difference in the recurrent cases of ketosis between the two groups within 6 months ( P>0.05) . Conclusions:The self-management intervention based on the shared decision-making model as the starting point may improve the level of diabetes knowledge, diabetes management self-efficacy and self-management behavior and stabilize the level of blood glucose of patients with diabetic acidosis.

OBJECTIVE: To observe and verify the key anatomies of DeLancey's three levels of vaginal support theory through laparoscopic surgery by space dissection technique. METHODS: The features and stress performance of related anatomies were observed and analyzed in laparoscopic type C hysterectomy and pelvic lymphadenectomy for cervical cancer by natural space exposures. RESULTS: The main ligament-like structure at level Ⅰ was the uterosacral ligament, which acted as the main apical fixation in the sacral direction, while the cardinal ligament was mainly composed of vascular system, lymph-vessels and loose connective tissue around them, lacking the tough connective tissue structures, which was connected to the internal iliac vascular system. There were no strong ligaments connected to the tendinous arch of pelvic fascia (ATFP) at the lateral side of vaginal wall at level Ⅱ. ATFP was the edge of the superior fascia of pelvic diaphragm, which was bounded by the fascia of the obturator. Its surface was smooth and close to the levator ani muscle and fuses with the vaginal fascia in about one thirds of middle lower segments of the vagina. When the ureter tunnel is separated, dense connective structures can be found in both anterior and posterior walls near the intersection of the ureter across uterine artery, fixing the bilateral angle of the bladder triangle, starting from the cervix and vagina and ending in the tunica muscularis vesicae urinariae. CONCLUSIONS Based on the laparoscopic anatomy, the pelvic floor fascia ligament support above the levator ani muscle can be considered mainly around the vagina, and fascial ligament above the levator ani muscle can be simply considered as two parallel planes forming a "double hammock" structure, which may provide more anatomic data for pelvic floor reconstruction.
Female ; Humans ; Laparoscopy ; Ligaments ; anatomy & histology ; Pelvic Floor ; Urinary Bladder ; Vagina ; anatomy & histology ; surgery

Objective: The aim of this retrospective study was to evaluate the prognostic significance of pretreatment Neutrophil-to-Lymphocyte Ratio(NLR) in locally advanced non-small cell lung cancer(NSCLC) patients treated with thoracic radiotherapy. Methods: We retrospectively analyze 420 patients who received thoracic radiotherapy alone, sequential chemoraiotherapy or concurrent chemoradiotherapy for locally advanced stage NSCLC from January 2007 to December 2010 of our hospital. The patients were divided into two groups (high NLR group and low NLR group) with appropriate cutoff point using the receiver operating characteristic (ROC) curve method. The survival curve was established by Kaplan-Meier method. The Log-rank test was used to compare the survival of the two NLR groups and the multivariate analysis was carried out by Cox regression model. Results: Among the 420 patients, 99 received radiotherapy alone, 139 received sequential chemoradiotherapy and 182 received concurrent chemoradiotherapy. 345 patients died and 75 were still alive. The median follow-up time was 5.2 years and the median overall survival was 22 months. The cut-off value of pretreatment NLR was 2.1. The 5-year PFS and OS rates in high NLR group and low NLR group were 10.6% vs 15.7% (P=0.033) and 15.5% vs 22.7% (P=0.012). Multivariate analysis confirmed that pretreatment NLR (hazard ratio 1.06, P=0.041) was independent prognostic factor of OS. Conclusions Our study revealed that the pretreatment NLR is the independent prognostic factor of OS in patients with locally advanced stage NSCLC treated with thoracic radiotherapy. However, NLR is still greatly influenced by patient′s condition and treatment which needs further research.

ObjectiveTo explore the effects of companion support on insulin pump therapy in adolescents with type 1 diabetes.Methods A total of 60 patients were randomly divided into experimental group and control group,30 cases respectively. Patients in control group were given routine education,while patients in experimental group received additional intervention of companion support. Changes of blood glucose,the occurrence of negative events during the use of insulin pump and standardized usage of insulin pump were compared between two groups. Blood glucose before sleep in one random day was recorded and the fluctuation of blood glucose was compared between two groups.Results After six months,fasting and postprandial blood glucose,glycated hemoglobin and the occurrence of negative events during the use of insulin pump in experimental group were significantly lower than those in control group (P<0.05). The waveform stability at one random day before sleep of experimental group was better than that of control group.Conclusions Companion support plays curial roles in controlling blood glucose, improves the standardization of insulin pump operation and effectively reduces the negative events in adolescents with type 1 diabetes undergoing temporary insulin pump therapy.