Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnor-malities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms under-lying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Uti-lizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expres-sion QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4 110,NControls=13 569),we imple-mented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Associa-tion Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD patho-genesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate＜0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were asso-ciated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were asso-ciated with CJD at the transcriptional level.

Objective To explore the impact of an intelligent puncture navigation used by different physicians with varying years of experience to perform the lung puncture biopsy surgery.Methods A retrospective selection was conducted of 182 patients who completed lung puncture biopsy surgery.The primary parameters were recorded included puncture time,the number of needle adjust-ments,dose length product(DLP),and complications.The physicians were categorized into high-experience and low-experience groups based on their years of clinical practice.The differences of navigation guidance and manual puncture were compared between the two groups.Results The use of navigation guidance significantly reduced the procedure time for both groups of physicians(P<0.05).Additionally,for the low-experience group,navigation guidance notably decreased the number of needle adjustments(P<0.05)and reduced the radiation dose received by patients(P<0.05).Conclusion The application of intelligent puncture navigation can shorten the procedure time,reduce the number of needle adjustments,and lower the radiation dose received by patients in lung puncture biopsy procedures.It also bridges the operational performance gap between low-experience and high-experience physicians,making it a val-uable imaging-guided tool for widespread adoption.

Objective:To investigate whether exosome-derived microRNA (miR)-877-5p can affect the malignant biological behaviors of glioma cells by regulating transmembrane 4 superfamily member 1 (TM4SF1).Methods:(1) Tumor tissues and corresponding adjacent tissues from 42 patients with glioma who underwent surgical resection in Department of Neurosurgery, the First Affiliated Hospital of Nanyang Medical College from September 2024 to February 2025 were collected. The miR-877-5p and TM4SF1 mRNA expressions in tumor tissues and corresponding adjacent tissues were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the correlation between miR-877-5p and TM4SF1 mRNA expressions in tumor tissues was analyzed by Pearson correlation. (2) HEB, U87, LN229, and U251 cells at the logarithmic growth phase were cultured and their miR-877-5p and TM4SF1 mRNA expressions were detected by qRT-PCR. Exosomes from U87, LN229, and U251 cells were isolated, and their morphology was observed under a transmission electron microscope; protein expressions of CD9, CD63, tumor susceptibility gene 101 (TSG101), and Calnexin in exosomes were detected by Western blotting. The miR-877-5p expression in exosomes of U87, LN229, and U251 cells was detected by qRT-PCR. The diameter of exosomes from LN229 cells was measured using a Malvern Zetasizer particle size and zeta potential analyzer, and the uptake efficiency of exosomes in LN229 cells was detected by flow cytometry. LN229 cells were divided into a normal control group, a miR-877-5p negative control group, a miR-877-5p mimic group, a miR-877-5p mimic+pcDNA empty vector group, and a miR-877-5p mimic+pcDNA-TM4SF1 group; except for the normal control group, the other groups were transfected with corresponding plasmids through exosomes and cultured for 24 hours; and then, miR-877-5p mRNA expression was detected by qRT-PCR; cell viability was detected by CCK-8 assay, cell apoptosis was detected by flow cytometry, cell invasion was detected by Transwell assay, and TM4SF1, Cyclin D1, Bcl-2 associated X protein (Bax), and matrix metalloproteinase 2 (MMP2) protein expressions and expressions of TM4SF1 downstream pathway proteins phosphorylated protein kinase B (p-AKT) and β-catenin were detected by Western blotting. The targeting relation between miR-877-5p and TM4SF1 was validated using a dual-luciferase reporter assay. A U251 cell experiment was performed for universal verification: U251 cells were divided into a normal control group, a miR-877-5p negative control group, a miR-877-5p mimic group, a miR-877-5p mimic+pcDNA empty vector group, and a miR-877-5p mimic+pcDNA-TM4SF1 group; cell apoptosis was detected by flow cytometry, and TM4SF1 protein expression was detected by Western blotting. (3) Eighteen male BALB/c nude mice were randomly divided into a control group, a miR-877-5p mimic group, and a miR-877-5p mimic+pcDNA-TM4SF1 group, with 6 mice in each group; 100 μL LN229 cell suspension, LN229 cell suspension transfected with miR-877-5p mimic, and LN229 cell suspension transfected with miR-877-5p mimic and pcDNA-TM4SF1 were, respectively, subcutaneously injected into the lateral abdomen of nude mice in these 3 groups. After 28 days of feeding, the mass and volume of the transplanted tumors were measured, and the TM4SF1, Cyclin D1, Bax, and MMP2 protein expressions in the transplanted tumors were detected by Western blotting. Results:(1) Compared with that in the corresponding adjacent tissues, miR-877-5p mRNA expression in the tumor tissues was significantly decreased and TM4SF1 mRNA expression was statistically increased ( P<0.05). Correlation analysis showed that the miR-877-5p and TM4SF1 mRNA expressions in the tumor tissues were negatively correlated ( r=-0.966, P<0.001). (2) Compared with those in the HEB cells, statistically decreased miR-877-5p mRNA expression and increased TM4SF1 mRNA expression in U87, LN229, and U251 cells were noted ( P<0.05). Under the transmission electron microscope, the exosomes in glioma cells were all biconcave disc-shaped and had a complete lipid bilayer membrane structure. Western blotting indicated positive CD9, CD63, and TSG101 protein expressions and negative Calnexin protein expression in the exosomes of glioma cells. Flow cytometry results indicated a relatively high uptake efficiency of exosomes in LN229 cells. Compared with that in the U87 and U251 cells, the miR-877-5p mRNA expression in exosomes of LN229 cells was significantly decreased ( P<0.05). The diameter of exosomes in LN229 cells was 80-150 nm. Compared with the miR-877-5p negative control group, the miR-877-5p mimic group had an increased miR-877-5p mRNA expression, decreased cell survival rate (negative control group: [95.43±0.23]%; miR-877-5p mimic group: [51.24±5.67]%), increased cell apoptosis rate ([3.34±0.22]% vs. [35.24±4.17]%), reduced number of invasive cells ([127.33±13.63] cells per high-power field vs.[59.67±6.87] cells per high-power field), downregulated TM4SF1, Cyclin D1 and MMP2 protein expressions, upregulated Bax protein expression, and decreased p-AKT and β-catenin protein expressions, with significant differences ( P<0.05). Compared with the miR-877-5p mimics+pcDNA empty vector group, the miR-877-5p mimic+pcDNA-TM4SF1 group had a decreased miR-877-5p expression, increased cell survival rate (miR-877-5p mimics+pcDNA empty vector group: [56.27±5.24]%; miR-877-5p mimic+pcDNA-TM4SF1 group[75.31±8.13]%), decreased cell apoptosis rate ([36.27±4.42]% vs. [15.37±1.73]%), increased number of invasive cells ([62.67±6.14] cells per high-power field vs. [95.50±10.58] cells per high-power field), upregulated TM4SF1, Cyclin D1 and MMP2 protein expressions, decreased Bax protein expression, and upregulated p-AKT and β-catenin protein expressions, with significant differences ( P<0.05). Dual-luciferase assay results showed that in the plasmids carrying wild-type TM4SF1 sequence, the luciferase activity in the miR-877-5p mimics group was significantly lower than that in the miR-877-5p negative control group ( P<0.05); in the plasmids carrying the mutant TM4SF1 sequence, no significant change in the luciferase activity was noted between the miR-877-5p negative control group and miR-877-5p mimic group ( P>0.05). Universal verification results: in U251 cells, compared with the miR-877-5p negative control group, the miR-877-5p mimic group had a significantly increased cell apoptosis rate and a statistically decreased TM4SF1 protein expression ( P<0.05); compared with the miR-877-5p mimic+pcDNA empty vector group, the miR-877-5p mimic+pcDNA-TM4SF1 group showed significantly decreased apoptosis rate and statistically increased TM4SF1 protein expression ( P<0.05). (3) Compared with the normal control group, the miR-877-5p mimic group had statistically reduced tumor mass and volume, significantly decreased TM4SF1, Cyclin D1 and MMP2 protein expressions, and significantly increased Bax protein expression ( P<0.05). Compared with the miR-877-5p mimic group, the miR-877-5p mimic+pcDNA-TM4SF1 group had significantly increased tumor mass and volume, statistically increased TM4SF1, Cyclin D1 and MMP2 protein expressions, and statistically decreased Bax protein expression ( P<0.05). Conclusion:Exosome-derived miR-877-5p may inhibit the proliferative and invasive capacities of glioma cells and promote cell apoptosis by targetedly inhibiting the TM4SF1 expression, thereby exerting an anti-tumor effect.

Objective:To analyze the prospective associations between liver biomarkers and mortality among Chinese middle-aged and elderly populations and to evaluate the mortality risk predictive value.Methods:A total of 22 758 participants from the 3 rd resurvey of the China Kadoorie Biobank were included. Cox proportional hazard models were used to analyze the prospective associations of 5 liver biomarkers with mortality. These liver biomarkers included two liver imaging biomarkers (liver fat attenuation parameter, liver stiffness measurement) and three serum liver enzyme biomarkers [gamma-glutamyl transferase (GGT), ALT, and AST]. Restricted cubic spline was used to assess the nonlinear associations between biomarkers and mortality. The area used the receiver operating characteristic curve (AUC) to evaluate the predictive ability of the models after incorporating liver biomarkers into traditional prediction models for mortality. Results:The mean age of the participants was (65.2±9.1) years, with a median follow-up of 1.5 years, during which 307 deaths occurred. Compared to individuals without hepatic steatosis, those with severe hepatic steatosis had a 79% higher risk of mortality, with a HR of 1.79 (95% CI: 1.06-3.03). Compared to individuals without hepatic fibrosis, those with advanced fibrosis and cirrhosis had higher mortality risks of 48% and 91%, respectively (both P<0.05). For each standard deviation increase in GGT, the mortality risk increased by 10% ( HR=1.10, 95% CI: 1.05-1.15), with the positive association plateauing at higher GGT levels. AST exhibited a U-shaped association with mortality risk. The AUC of the prediction model adding liver biomarkers into traditional prediction factors was 0.718 (95% CI: 0.679-0.757), with an increase of 0.030 ( P<0.001) compared with the traditional model. Conclusions:Severe hepatic steatosis, higher levels of hepatic fibrosis, and elevated GGT levels are significantly associated with higher mortality risk. AST shows a U-shaped nonlinear association with mortality risk. Incorporating liver biomarkers into traditional risk prediction models enhance the ability to predict mortality.

Objective:To investigate the prospective associations between plasma metabolites and the risks of all-cause and cause-specific mortality among Chinese adults.Methods:This study analyzed plasma metabolomics data from 2 183 healthy adults in the China Kadoorie Biobank (CKB), measured using targeted mass spectrometry. Cox proportional hazards regression models were used to examine the associations between 630 metabolites and the risk of all-cause mortality. Cause-specific hazard regression models evaluated the associations between metabolites and cardiovascular disease (CVD) risks, cancer, and other-cause mortality. Stepwise regression was used to identify key metabolites independently associated with all-cause mortality, and the area under the receiver operating characteristic curve (AUC) was calculated to assess the improvement in predictive performance when these metabolites were added to traditional risk prediction models.Results:The mean age of the participants was (53.2±9.8) years, 65.1% of whom were female. During a median follow-up of 14.5 years, 231 deaths occurred. A total of 44 metabolites were significantly associated with the risk of all-cause mortality [false discovery rate (FDR)-adjusted P<0.05], primarily including triglycerides, ceramides, and amino acids. Additionally, 29 and 15 metabolites were found to be associated with cancer and other-cause mortality, respectively, but no metabolites were significantly associated with CVD mortality after FDR corrections. Adding 14 metabolites independently associated with all-cause mortality into the traditional prediction model significantly improved its predictive performance. Specifically, incorporating metabolites into the traditional model, which already included laboratory biomarkers, increased the AUC to 0.798 (95% CI: 0.755-0.843), an improvement of 0.088 compared to the traditional model ( P<0.001). Conclusions:Multiple metabolites are significantly associated with mortality risk and can substantially improve the accuracy of mortality risk prediction models. These findings provide new insights into the physiological mechanisms of aging and offer valuable clues for personalized health risk assessment.

Objective:To evaluate the effect of ciprofol on intraoperative hypotension in patients undergoing bronchoscopy procedures.Methods:In this randomized controlled study, 112 adult patients of either sex, aged 18-64 yr, with a body mass index of 19.8-28.3 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with estimated operation time of ≥1 h, undergoing elective bronchoscopy procedures, were assigned to one of two groups ( n=56 each) using a random number table method: ciprofol group (C group) and propofol group (P group). All the patients received total intravenous anesthesia. The induction dose of ciprofol was 0.1-0.3 mg/kg, and the maintenance dose was 0.4-1.2 mg·kg -1·h -1 in group C. The induction dose of propofol was 1-3 mg/kg, and the maintenance dose was 4-12 mg·kg -1·h -1 in group P. The primary outcome was the incidence of intraoperative hypotension, and the secondary outcomes were the time of emergence from anesthesia, sleep quality, patients′ and surgeons′ satisfaction with anesthesia, and the incidence of complications within 30 days after surgery. Results:Compared with group P, the incidence of intraoperative hypotension was significantly decreased, and the time of emergence from anesthesia was shortened in group C ( P<0.05). There was no statistically significant difference in secondary outcomes between the two groups ( P>0.05). Conclusions:Ciprofol is superior to propofol in reducing the risk of intraoperative hypotension and facilitates a more rapid emergence from anesthesia in patients undergoing bronchoscopy procedures.

Objective:To explore the clinical application value of convolutional neural network（CNN）based on deep learning in the automatic measurement of dynamic pelvic floor ultrasound video parameters and the diagnosis and classification of cystocele.Methods:A retrospective analysis was conducted on dynamic pelvic floor ultrasound videos from 398 postpartum women who underwent examinations at the First People's Hospital of Foshan between June 2020 and June 2022. The lowest point of the posterior bladder wall（PWB），urethral rotation angle（URA），and retrovesical angle（RVA）were manually measured by a senior radiologist（R1）and a junior radiologist（R2），and cystocele was classified according to the Green standard. The CNN model was employed to automatically extract the above parameters and to diagnose and classify cystocele. Using R1 measurements as a reference，intraclass correlation coefficient（ICC）was used to evaluate the consistency between the CNN model and R1，as well as between R2 and R1. The Kappa value was used to assess the agreement between the CNN model，R2，and R1 in the diagnosis and classification of cystocele. Additionally，the time consumption of the three measurement methods was compared.Results:The CNN model showed good consistency with R1 in measuring PWB and URA（ICC = 0.983，0.894），while its consistency in measuring RVA was moderate（ICC = 0.614）. The ICC between R2 and R1 in measuring PWB，URA，and RVA was 0.979，0.815，and 0.627，respectively. In the measurement of PWB and URA，the consistency between the CNN model and R1 was superior to that between R2 and R1. For cystocele diagnosis，the Kappa value between the CNN model and R1 was 0.924，which was higher than that between R2 and R1（0.904）. In cystocele classification，the Kappa value between the CNN model and R1 was 0.503，also higher than that between R2 and R1（0.426）. The CNN model processed a single video in 2.5（0.6）s，significantly faster than R1［59.9（16.9）s］and R2［56.8（11.2）s］（all P < 0.001）. Conclusions:The CNN model demonstrates high accuracy and efficiency in the measurement，diagnosis，and classification of cystocele，outperforming a junior radiologist and showing potential for clinical application.

Objective:To investigate the clinical efficacy of anterolateral thigh free fat flap (hereinafter referred to as fat flap) transplantation with vascular anastomosis for reconstructing facial depressed scars.Methods:This study was a retrospective observational study. Twelve patients (5 males and 7 females, aged 15-67 years) with facial depressed scars who met the inclusion criteria were treated at the First Affiliated Hospital of Air Force Medical University from June 2017 to September 2023. Before surgery, the patient and observer scar assessment scale (POSAS) was used to evaluate the facial scar condition of the patients. Scar depression area was measured ranging from 5 cm×4 cm to 14 cm×7 cm, with a depth from 6 to 12 mm. All cases were reconstructed with fat flaps. The harvested fat flaps ranged 6 cm×5 cm to 15 cm×8 cm in size, with vascular pedicle lengths ranging from 4 to 7 cm. Intraoperatively, the number of perforator vessels observed was as follows: 1 perforator in 2 cases, 2 perforators in 7 cases, and 3 perforators in 3 cases. Fat flaps were transplanted to the recipient sites, with the main trunks of its perforator vessels and accompanying veins anastomosed to the recipient arteries and veins. Donor site wounds were closed primarily. Postoperatively, the survival of fat flap, vascular crisis, and the healing of donor site incision were observed. During follow-up, the facial contour was observed, the long-term reintervention at recipient sites was recorded, and the scars formed at both donor and recipient incisions were observed. The function of donor limb was assessed. At the last follow-up, the scar condition at recipient site was evaluated using the two subscales of POSAS (the observer scale and the patient self-rating scale), respectively.Results:One patient developed a mild hematoma due to bleeding within 24 hours after surgery. After timely removal of the hematoma and enhanced drainage, the fat flap survived. The fat flaps of the other patients survived completely with no vascular crisis occurred. The donor site incision of 1 patient developed infection 7 days after surgery and healed after timely dressing changes, while the donor site incisions of the remaining patients all healed smoothly. During the follow-up of 6-26 months, significant improvement in facial symmetry was observed in all patients, with natural fullness achieved. Autologous microlipofilling was performed in 2 patients at 6 months and 10 months postoperatively, respectively. Local liposuction contouring was conducted in 1 patient at 12 months postoperatively. The scars at the donor and recipient sites were mild. No functional impairment at donor sites was recorded, and the motor and sensory functions of the affected limbs were normal. At the last follow-up, the observer scale assessment showed that the scores for vascularity, thickness, roughness, pliability, pigmentation, and overall assessment of the scars in the recipient areas were 2.1±0.5, 1.9±0.7, 3.0±0.7, 2.1±1.2, 3.8±1.1, and 2.8±0.5, respectively, which were significantly lower than 4.2±0.9, 5.1±1.0, 4.2±1.5, 4.6±1.4, 4.8±1.2, and 5.2±1.0 before surgery (with t values of 7.24, 11.70, 4.31, 9.57, 4.17, and 9.30, respectively, P<0.05). The patient self-rating scale assessment showed that the scores for pain, pruritus, color, stiffness, irregularity, thickness, and overall satisfaction of the scars in the recipient areas were 1.3±0.5, 1.3±0.4, 1.9±1.0, 2.3±1.1, 1.8±0.8, 1.9±0.8, and 1.9±0.7, respectively, which were significantly lower than 2.9±1.0, 2.6±0.9, 4.2±1.5, 5.3±2.0, 4.0±1.2, 4.6±1.3, and 4.8±1.4 before surgery (with t values of 6.09, 5.20, 8.07, 9.17, 8.00, 8.60, and 8.81, respectively, P<0.05). Conclusions:Transplantation of the fat flaps with vascular anastomosis can safely and effectively reconstruct facial depressed scars, and significantly improve the aesthetic contour and scar-related symptoms. This technique yields stable long-term outcomes with high patient satisfaction, demonstrating high value of clinical application.

Objective:To explore the clinical significance of trisomy 7 signaled by non-invasive prenatal testing (NIPT).Methods:Pregnant women with high risk for trisomy 7 by NIPT from January 2017 to December 2023 were selected as the study subjects, and the results of prenatal diagnosis and follow-up were analyzed. Literature related to pregnant women with a high risk for trisomy 7 by NIPT from January 2016 to July 2024 was retrieved from China Biomedical Literature Database, Wanfang Database, China National Knowledge Infrastructure and PubMed database. Relevant information such as the incidence of trisomy 7 by NIPT, positive predictive value (PPV), and pregnancy outcomes were collected. This study has been approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No. JS2022010).Results:A total of 51 women with a high risk for trisomy 7 by NIPT were identified. Thirty-two of them had chosen chromosomal microarray analysis (CMA) of amniotic fluid cells, and 1 case of mosaic trisomy 7 was detected, which had yielded a PPV of 3.13%. Four women had opted termination of pregnancy, 1 had miscarriage, 4 had pre-term and/or low weight birth, whilst the remaining 42(82.4%) had full-term delivery. In total 19 literature were retrieved, which had involved 278 cases of trisomy 7 signaled by NIPT, among which 5 fetuses with mosaic trisomy 7 (3.14%) were confirmed. Among the 211 women with follow-up outcomes, 2 (0.95%) had intrauterine growth restriction, 3 (1.42%) had abnormal fetal structure detected by ultrasound, 2 (0.95%) had miscarriage, 9 (4.27%) underwent pregnancy termination, 28 (13.27%) had preterm and/or low weight birth, whilst 167 (79.14%) had normal delivery. In 18 cases, chromosomal analysis of placental tissue was carried out, and 17 were confirmed to have mosaicism trisomy 7.Conclusion:The PPV for trisomy 7 signaled by NIPT is extremely low. Although most of such women had a full term delivery, adverse pregnancy outcomes may still occur in a minority of cases. Clinicians should provide adequate genetic counseling for such women and recommend appropriate prenatal diagnosis strategies and optimal perinatal management plans.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.