The prevalence of female pelvic floor dysfunction (PFD) ranges from 17.8% to 74.07%, with approximately 30% of patients experiencing comorbid anxiety, depression, or other psychological disorders, severely impairing their quality of life. Current assessment methods for PFD are primarily based on clinical techniques such as the pelvic organ prolapse quantification and two-dimensional ultrasound. But they are limited by high subjectivity, operational complexity, and the inability to provide real-time dynamic evaluation. In recent years, emerging technologies including high-density electromyography, three-dimensional ultrasound, specific biomarkers, and artificial intelligence have complemented conventional clinical methods by providing dynamic functional data and molecular-level evidence, achieving multidimensional “structure-function-molecular”assessment of PFD. The relevant literature on PFD assessment published in CNKI, PubMed, and other databases from 2019 to 2024 were retrieved. The current application status and value of commonly used clinical techniques, the core characteristics of emerging technology assessments, and the integration path between the two were reviewed, so as to provide the evidence for individualized diagnosis and treatment of PFD.

ObjectiveTo assess the microstructural involvement of gray matter in recovered COVID-19 patients using Synthetic MRI. MethodsThis study was conducted in 29 recovered COVID-19 patients， including severe group （SG， n=11） and ordinary group （OG， n=18）. Healthy volunteers matched by age， sex， BMI and years of education were selected as a healthy control group （HC=23 cases）. Each subject underwent synthetic MRI to generate quantitative T₁ and T₂ maps， and the T₁ and T₂ maps were segmented into 90 regions of interest （ROIs） using automatic anatomical labeling （AAL） mapping. T₁ and T₂ values for each ROI were obtained by averaging all voxels within the ROIs. The T₁ and T₂ values of the 90 brain regions between the three groups were compared. ResultsRelative to HC， the SG had significantly higher T2 values in bilateral orbital superior frontal gyrus， bilateral parahippocampal gyrus， bilateral putamen， bilateral middle temporal gyrus， bilateral Inferior temporal gyrus， left orbital superior frontal gyrus， left orbital inferior frontal gyrus， left gyrus rectus， left anterior cingulate and paracingulate gyri， right median cingulate and paracingulate gyri， left posterior cingulate gyrus， and left supramarginal gyrus （P＜0.05）； Relative to OG， SG showed significantly increased T₂ values in the left rectus gyrus， left parahippocampal gyrus， bilateral middle temporal gyrus， and bilateral inferior temporal gyrus （P＜0.05）. Relative to HC， the T₁ values of SG were significantly increased in bilateral orbital superior frontal gyrus， left rectus gyrus， left anterior cingulate and paracingulate gyri， right posterior cingulate gyrus， left parahippocampal gyrus， left lingual gyrus， left putamen， left thalamus（P＜0.05）； Relative to OG， the T₁ values of SG were significantly higher in the right posterior cingulate gyrus， right calcarine fissure and surrounding cortex， and left putamen （P＜0.05）. ConclusionsEven after recovering from COVID-19， patients may still have persistent or delayed damage to their brain gray matter structure， which is correlated with the severity of the condition. SyMRI can serve as a sensitive tool to assess the extent of microstructural damage to the central nervous system， aiding in early diagnosis of the disease.

The number of investigator initiated research (IIR) is increasing. But the recognition and management of IIR in China is still in its infancy, and there is a lack of specific and operable guidance for the implementation process. Based on our practical experiences, previous literature reports, and current policy regulations, the authors took prospective IIR as an example to summarize the implementation process of IIR into 14 steps, which are as the following: study initiation, ethical review, study registration, study filing, case report form design, database establishment, standard operating procedure making, investigator training, informed consent, data collection, data entry, data verification, data locking and data archiving.

Objective    To investigate the use of opioid analgesics during the postoperative hospitalization in patients undergoing lung resection and analyse its influencing factors. Methods    The clinical data of 450 patients undergoing lung resection in Sichuan Cancer Hospital among a multicenter symptom research database (CN-PRO-Lung 1) between November 2017 and January 2020 were analyzed. There were 248 males and 202 females with an average age of 54.7±10.3 years. Results    A total of 448 (99.6%) patients used opioid analgesics. The average daily morphine equivalent dose during the postoperative hospitalization was 48.9 mg. There were statistical differences in postoperative morphine equivalent dose across patients with different sex, age, highest level of education, Charlson Comorbidity Index score, surgical approach, surgical type, operative time, postoperative hospital stay and grade of postoperative complications (all P<0.05). Multivariate analysis showed that sex, surgical approach and postoperative hospital stay were independent influencing factors for morphine use during the postoperative hospitalization in patients undergoing lung resection (all P<0.05). Conclusion    In clinical practice, attention should be paid to postoperative pain for male patients, as well as to promote the application of minimally invasive surgery, and to shorten the length of postoperative hospital stay, in order to ultimately reduce the use of opioids.

Immune deficiency of the host caused by allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the initial factor of reactivation of latent human cytomegalovirus (HCMV). The risk factors of reactivation of HCMV in allo-HSCT recipients consist of the serological status of HCMV in donors and recipients, the matching degree of human leukocyte antigen (HLA) and pretreatment patterns, etc. The reactivation of HCMV is associated with the expression of a series of viral cleavage and proliferation proteins induced by the overexpression of major immediate early promoter/enhancer (MIEP) in the viral genome. In this article, the risk factors of reactivation of HCMV after allo-HSCT, the molecular changes related to maintaining latent infection of HCMV, the key role of MIEP overexpression in reactivation of HCMV, and the molecular pathways involved in reactivation of HCMV after allo-HSCT were reviewed and the major molecular events of reactivation of HCMV after allo-HSCT were elucidated, aiming to provide reference for the prevention and treatment of cytomegaloviral disease (CMVD) after allo-HSCT.

Chaperone-mediated autophagy (CMA) is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, the mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, a drug that is commonly the first medication prescribed for type 2 diabetes, can induce CMA. We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation. Notably, we find that amyloid-beta precursor protein (APP) is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner. The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity. Importantly, we find that in the APP/PS1 mouse model of Alzheimer's disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβ plaque levels and reverses the molecular and behavioral AD phenotypes. Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.

In the original publication Fig. 1D and supplementary material is incorrect. The correct figure and supplementary material is provided in this correction.

One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem (ES) cells, which is used to produce gene-targeted mice for wide applications in biomedicine. However, a major bottleneck in this approach is that the robustness of germline transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing, which impairs the efficiency and robustness of mouse model generation. Recently, we have established a new type of pluripotent cells termed extended pluripotent stem (EPS) cells, which have superior developmental potency and robust germline competence compared to conventional mouse ES cells. In this study, we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term passage. Based on gene targeting in mouse EPS cells, we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation, which could be accomplished in approximately 2 months. Importantly, using this approach, we successfully constructed mouse models in which the human interleukin 3 (IL3) or interleukin 6 (IL6) gene was knocked into its corresponding locus in the mouse genome. Our study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting, which have great application potential in biomedical research.