Investigating the Impact of Tea Consumption on Cognitive Function and Exploring Tea-Genetic Interactions in Older Adults Aged 65-105 Years: Findings from the 2002-2018 CLHLS Data.

BACKGROUND: As the global population ages, cognitive impairment (CI) becomes more prevalent. Tea has been one of the most popular drinks in the world. Several studies have demonstrated that tea consumption has an impact on cognitive function. OBJECTIVE: This study aims to examine the association between tea consumption and cognitive function and explore the potential effect of genetics on the relationship between tea consumption and CI risk in older adults. DESIGN: This is a prospective longitudinal study using data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). SETTING: Six waves of data from CLHLS containing 76,270 subjects were analyzed. Generalized estimation equations (GEE) with a logit link function were adopted to estimate the effect of tea consumption on CI risk from a cross-sectional and longitudinal perspective. PARTICIPANTS: A population-based cohort of adults aged 65-105 years. MEASUREMENTS: The frequency and type of tea consumption were obtained by questionnaires. CI was measured based on MMSE. Polygenic risk was measured using the polygenic score approach described by the International Schizophrenia. RESULTS: The results showed that drinking green tea had a better protective effect on cognitive function than other types of tea, the incidence of CI gradually decreased with the increase of tea consumption frequency, and men were more likely to benefit from tea consumption. Additionally, we also found a significant interaction between tea consumption and genetic risk, measured by polygenic risk score (PRS). CONCLUSIONS: Based on current research evidence, tea consumption, may be a simple and important measure for CI prevention.

[The effect of the AIM2 inflammasome in noise-induced cognitive dysfunction in rats].

Objective: To explore the effect of the absent in melanoma 2 (AIM2) -mediated neuroinflammation in noise-induced cognitive dysfunction in rats. Methods: In April 2023, sixteen male Wistar rats were randomly divided into control group and noise group, with 8 rats in each group. The rats in the noise group were placed in 50 cm×50 cm×40 cm transparent boxes and exposed to 100 dB (A) white noise with a sound pressure level of 100 dB (A) (4 h/d for 30 d) . At the same time, rats in the control group were kept in similar boxes with environmental noise less than 60 dB (A) . After 30 days of noise exposure, the Morris water maze experiment was applied to test the learning and memory abilities of the rats; the pathological morphology of hippocampal tissues was observed by Hematoxylin-Eosin (HE) staining. Western blot was used to detect the protein expression levels of AIM2, cysteinyl aspartate specific proteinase-1 (caspase-1) , apoptosis-associated speck-like protein (ASC) , interleukin-1ß (IL-1ß) , IL-18, ionic calcium-binding articulation molecule-1 (Iba-1) , and glial fibrillary acidic protein (GFAP) . The expression of both Iba-1 and GFAP in hippocampal tissue was assessed by immunohistochemical staining. The co-localization of AIM2 with Iba-1 or GFAP was determined by immunofluorescence double staining. Results: Compared with the control group, the escape latency of rats in the noise group was increased by 16.29 s, 17.71 s, and 20.26 s on days 3, 4, and 5, respectively. On day 6, the noise-exposed rats spent shorter time in the target quadrant and had fewer times in crossing the platform[ (7.25±2.27) s and (1.13±0.64) times] than the control group[ (15.64±3.99) s and (4.25±2.12) times] (P<0.05) . After noise exposure, hippocampal neurons of rats displayed marked nuclear hyperchromatic and pyknosis phenomenon. The noise-exposed rats had higher numbers of both microglia and astrocytes (27.00±2.65 and 43.33±5.51) in the DG area of the hippocampus relative to the control group (14.67±3.06 and 20.00±4.58) (P<0.05) . Moreover, the glial cells in the noise group had larger cell cytosol with more and thicker branches. The protein expression levels of inflammatory cytokines Cleaved-IL-1ß and Cleaved-IL-18 in the hippocampus of rats in the noise group (1.55±0.19 and 1.74±0.12) were significantly higher than the control group (1.00±0.11 and 1.00±0.13) (P<0.05) . After noise exposure, the protein expression levels of AIM2, Cleaved-Caspase-1 and ASC (1.19±0.09, 1.34±0.07 and 1.14±0.01) were higher than the control group (1.00±0.07, 1.00±0.14 and 1.00±0.06) and differences between the two groups were statistically significant (P<0.05) . A significant increase in the number of cells co-localizing AIM2 with Iba-1 or GFAP in the noise group (28.67±4.04 and 40.67±5.13) compared with the control group (15.67±4.04 and 17.67±3.79) , and statistically significant differences were observed between the two groups (P<0.05) . Conclusion: Noise exposure may activate the AIM2 inflammasome in hippocampal glial cells of rats, releasing excessive inflammatory cytokines and causing neuroinflammation that damages neurons.

Air dispersal of multi-drug-resistant organisms including meticillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii and carbapenemase-producing Enterobacterales in general wards: surveillance culture of air grilles.

BACKGROUND: The environmental surveillance of air grilles in clinical areas has not been systematically analysed. METHODS: Samples were collected from frequently touched items (N = 529), air supply (N = 295) and exhaust (N = 184) grilles in six medical and 11 surgical wards for the cultures of multi-drug-resistant organisms (MDROs): meticillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenemase-producing Enterobacterales (CPE), and isolates were selected for whole-genome sequencing (WGS). The contamination rates were correlated with the colonization pressures of the respective MDROs. RESULTS: From 3rd October to 21st November 2023, 9.8% (99/1008) of the samples tested positive, with MRSA (24.2%, 24/99), CRAB (59.6%, 59/99) and CPE (2.0%, 2/99), being the only detected MDROs. The contamination rate in air exhaust grilles (26.6%, 49/184) was significantly higher than in air supply grilles (5.8%, 17/295; P<0.001). The contamination rate of air exhaust grilles with any MDRO in acute medical wards (73.7%, 14/19) was significantly higher than in surgical wards (12.5%, 4/32; P<0.001). However, there was no difference in the contamination rate of air exhaust grilles between those located inside and outside the cohort cubicles for MDROs (27.1%, 13/48 vs 28.8%, 30/104; P=0.823). Nevertheless, the weekly CRAB colonization pressure showed a significant correlation with the overall environmental contamination rate (r = 0.878; 95% confidence interval (CI): 0.136-0.986; P=0.004), as well as with the contamination rate in air supply grilles (r = 0.960; 95% CI: 0.375-0.999; P<0.001) and air exhaust grilles (r = 0.850; 95% CI: 0.401-0.980; P=0.008). WGS demonstrated clonal relatedness of isolates collected from patients and air exhaust grilles. CONCLUSIONS: Air grilles may serve as MDRO reservoirs. Cohort nursing in open cubicles may not completely prevent MDRO transmission through air dispersal, prompting the consideration of future hospital design.

[Association between the clustering of adverse childhood experiences and sleep quality in middle-aged and older Chinese adults].

Objective: To examine the association between the clustering of adverse childhood experiences (ACEs) and sleep quality in middle-aged and older Chinese adults. Methods: Data were from the Life History Survey in 2014 and the third wave follow-up survey in 2015 of China Health and Retirement Longitudinal Study (CHARLS). A total of 10 824 participants aged 45 years and above were included in this study. According to the number of ACEs, the participants were divided into four groups: 0, 1, 2-3 and≥4 ACEs. The multivariate logistic regression model was used to analyze the association of ACEs clustering with inappropriate sleep duration and poor sleep quality in middle-aged and older adults. Results: Among the 10 824 participants with an average age of (60.83±9.06) years, 5 211 (48.14%) were males. About 6 111 participants (56.64%) had inappropriate sleep duration, and 3 640 participants (33.63%) had poor sleep quality. After adjusting for covariates including gender, age, residence, marital status, education, household consumption, BMI, smoking, drinking, and depression in adulthood, compared with the 0 ACE group, the risk of inappropriate sleep duration was significantly increased in the 2-3 ACEs group and≥4 ACEs group, while ORs (95%CIs) were 1.26 (1.12-1.41) and 1.43 (1.23-1.66), respectively. The risk of poor sleep quality in the 2-3 ACEs group and≥4 ACEs group was also significantly higher than that in the 0 ACE group, while ORs (95%CIs) were 1.28 (1.12-1.46) and 1.53 (1.29-1.80), respectively. Conclusion: ACEs clustering in childhood could negatively affect sleep duration and quality in middle-aged and older Chinese adults.

Factors affecting resolution of oculomotor nerve palsy following endovascular embolization of posterior communicating artery aneurysms / Factores que influyen en el tratamiento de la parálisis oculomotora con embolización endovascular de aneurismas comunicantes posteriores

Purpose: To investigate the effect of endovascular embolization of posterior communicating artery (Pcom) aneurysms on concomitant oculomotor nerve palsy (OMNP) and factors affecting the effect of treatment. Materials and methods: Patients with the Pcom aneurysms concomitant with OMNP were retrospectively enrolled for endovascular treatment of the aneurysms. All patients had the endovascular management. The clinical effect, degree of OMNP, size of the aneurysm, type of treatment, subarachnoid hemorrhage (SAH), and time from onset to treatment were analyzed on the resolution of OMNP. Results: Ninety-six patients with 99 Pcom aneurysms were enrolled and treated endovascularly, with the success rate of 100%. Immediately after endovascular treatment, 75 aneurysms (75.75%) got complete occlusion, and 24 (24.24%) nearly complete occlusion. Followed up for 3–18 (mean 8.52 ± 0.56) months, complete resolution of the OMNP was achieved in 63 patients (65.63%), partial resolution in 21 (21.88%), and non-recovery in the other 12 (12.50%). The degree of OMNP at onset, SAH, and time from onset to treatment were significantly (P < 0.05) correlated with the resolution of OMNP. Univariate analysis revealed that younger age of the patient, degree of OMNP at onset, presence of subarachnoid hemorrhage, and time from disease onset to treatment were significantly (P < 0.05) associated with the recovery of OMNP. Multivariate analysis revealed that the younger age, degree of OMNP at onset, and time from disease onset to treatment were significantly (P < 0.05) associated with the recovery of OMNP. Conclusion: Endovascular embolization of Pcom aneurysms concomitant with OMNP can effectively improve the OMNP symptoms, especially for patients with moderate and a shorter history of OMNP. Younger age, degree of oculomotor nerve palsy at onset, and time from onset to treatment may significantly affect recovery of oculomotor nerve palsy.(AU)

Objetivo: Investigar la eficacia de la embolización intravascular del aneurisma de comunicación posterior (Pcom) en pacientes con parálisis oculomotora (OMNP) y los factores que influyen en la eficacia. Materiales y métodos: Se analizaron retrospectivamente los datos clínicos de la terapia intravascular en pacientes con aneurismas Pcom con OMNP. Todos los pacientes recibieron tratamiento intravascular. Se analizaron los efectos de la eficacia clínica, el grado de OMNP, el tamaño del aneurisma, el método de tratamiento, la hemorragia subaracnoidea y el tiempo desde el inicio hasta el tratamiento en la regresión de OMNP.Resultados: Un total de 96 pacientes con 99 aneurismas Pcom fueron tratados con éxito. Inmediatamente después del tratamiento intravascular, 75 casos (75,75%) de aneurismas fueron completamente ocluidos y 24 casos (24,24%) casi completamente ocluidos. Durante el seguimiento de 3 a 18 meses (promedio: 8,52 ± 0,56 meses), se logró la resolución completa en 63 casos (65,63%), la resolución parcial en 21 (21,88%) y la no recuperación en los otros 12 (12,50%). El grado de OMNP al inicio, la hemorragia subaracnoidea y el tiempo de inicio a tratamiento se correlacionaron significativamente con la resolución de la OMNP (p < 0,05). El análisis univariado mostró que la menor edad del paciente, el grado de OMNP, la presencia de hemorragia subaracnoidea y el tiempo transcurrido desde el inicio de la enfermedad hasta el tratamiento se correlacionaron significativamente con la recuperación de OMNP (p < 0,05). Conclusión: La embolización intravascular del aneurisma Pcom combinada con OMNP puede mejorar eficazmente los síntomas de OMNP, especialmente en pacientes con OMNP a corto y mediano plazo. La edad temprana, el grado de parálisis del nervio oculomotor al inicio y el tiempo desde el inicio hasta el tratamiento tuvieron un efecto significativo en la recuperación de la parálisis del nervio oculomotor.(AU)

[Clinical outcome of posterior lumbar interbody fusion combined with Ponte osteotomy for reconstruction of coronal sagittal plane balance in degenerative scoliosis].

Objective: To evaluate the clinical efficacy of posterior lumbar interbody fusion combined with Ponte osteotomy in the treatment of patients with degenerative scoliosis. Methods: The medical records and imaging data of degenerative scoliosis in department of orthopedics, Peking Union Medical College Hospital from 2013 to 2022 were retrospectively collected, and the shortest follow-up time was 1 year. A total of 38 patients were included, including 13 males and 25 females, aged 50-87(65.6±10.9) years old.The follow-up was12-119(43±20) months. Standing position full spine anteroposterior lateral X-ray examinations were performed on all patients preoperatively, postoperatively, and at latest follow-up. The length of hospital stay, complications, operation time, blood loss, instrumented segment, fusion segmen were recorded. The clinical scores and coronasagittal imaging indicators at three time points were compared. Results: The operation time was (274.5±70.5)min, and intraoperative blood loss was (619.2±93.5)ml. The coronal vertical axis was improved from (2.9±1.8)cm preoperatively to (1.2±1.0)cm postoperatively. The preoperative coronal Cobb angle was 16.6°±9.9° and the immediate postoperative correction was 6.4°±4.0°(t=-6.83, P<0.001). The difference was statistically significant (t=-6.12, P<0.001). The coronal Cobb Angle at the last follow-up was 5.7°±3.7°, and there was no significant orthopaedic loss at the last follow-up (t=-6.12, P<0.001).The sagittal vertical axis decreased from (5.6±3.9)cm preoperatively to (3.2±2.5) cm immediately after operation (t=-6.83,P<0.001), and was well maintained at the last follow-up[(2.7±1.8) cm,t=-7.77,P<0.001]. Lumbar lordosis increased from 21.8°±10.2° preoperatively to 35.8°±8.3° postoperatively(t=12.01, P<0.001)and 40.1°±8.6° at last follow-up(t=-10.21, P<0.001). Oswestry disability score (ODI score), visual analogue score (VAS) low back pain score and VAS leg pain score were also lower after surgery than before surgery (all P<0.05). Conclusion: Posterior lumbar interbody fusion combined with Ponte osteotomy can significantly improve the coronal and sagittal plane deformity and postoperative functional score in adult patients with degenerative scoliosis.

[A study on the distribution characteristics of peripheral retinal defocus in children and adolescents].

Objective: To explore the distribution characteristics of peripheral retinal defocus in children and adolescents. Methods: This cross-sectional study included 500 individuals aged 3 to 18 years, who visited the People's Hospital of Lincang, the First Affiliated Hospital of Dali University and Dali Ophthalmology Hospital between January and December 2021. Data of the right eye of each participant was analyzed. There were 226 males (45.20%) and 274 females (54.80%), with an average age of (10.79±3.79) years. All participants underwent post-cycloplegic refraction, optical biometry, and intraocular pressure measurement to obtain spherical equivalent, average corneal curvature, axial length, and intraocular pressure. Multispectral refraction topography was performed to obtain topographic maps and values at various field angles and orientations of peripheral retinal defocus. Based on multispectral refraction topography, peripheral retinal defocus values were categorized as crater type, hemilateral upturn type, saddle type, and relatively flat type. The distribution of different refractive states was analyzed. Results: The spherical equivalent of the 500 participants was(-1.51±2.61) D, axial length was (24.10±1.28) mm, and average corneal curvature was (43.20±1.22) D. Among the 500 eyes, 382 exhibited hyperopic peripheral retinal defocus values, with 316 eyes (82.72%) being myopic. Myopic peripheral retinal defocus values were observed in 118 eyes, with 15 eyes (12.72%) being myopic. Among different types of peripheral retinal defocus values, 112 eyes (22.4%) exhibited a crater type, 153 eyes (30.6%) exhibited a hemilateral upturn type, 107 eyes (21.4%) exhibited a saddle type, and 128 eyes (25.6%) exhibited a flat type. The proportion of myopia was 82.14% (92 eyes), 69.28% (106 eyes), 60.75% (65 eyes), and 3.90% (5 eyes), respectively. The peripheral retinal defocus values at 15°, 30°, and 45° were (0.01±0.08) D, (0.06±0.21) D, and (0.20±0.37) D, respectively. The peripheral retinal defocus values at temporal, inferior, nasal, and superior locations were (0.58±0.69) D, (0.52±0.63) D, (0.21±0.64) D, and (-0.26±0.67) D, respectively. Notably, the superior primarily manifested as myopic, while the others were predominantly hyperopic. Conclusions: Approximately three-fourths of children and adolescents exhibit hyperopic peripheral retinal defocus values, with a higher prevalence of myopia in this subgroup. The hyperopia peripheral retinal defocus value increases with the distance from the retina to the macula. The peripheral retinal defocus values between superior and inferior, nasal and temporal locations are asymmetrical, with the temporal hyperopic peripheral retinal defocus value being most prominent and the superior myopic peripheral retinal defocus value being most evident.

Factors affecting resolution of oculomotor nerve palsy following endovascular embolization of posterior communicating artery aneurysms.

PURPOSE: To investigate the effect of endovascular embolization of posterior communicating artery (Pcom) aneurysms on concomitant oculomotor nerve palsy (OMNP) and factors affecting the effect of treatment. MATERIALS AND METHODS: Patients with the Pcom aneurysms concomitant with OMNP were retrospectively enrolled for endovascular treatment of the aneurysms. All patients had the endovascular management. The clinical effect, degree of OMNP, size of the aneurysm, type of treatment, subarachnoid hemorrhage (SAH), and time from onset to treatment were analyzed on the resolution of OMNP. RESULTS: Ninety-six patients with 99 Pcom aneurysms were enrolled and treated endovascularly, with the success rate of 100%. Immediately after endovascular treatment, 75 aneurysms (75.75%) got complete occlusion, and 24 (24.24%) nearly complete occlusion. Followed up for 3-18 (mean 8.52±0.56) months, complete resolution of the OMNP was achieved in 63 patients (65.63%), partial resolution in 21 (21.88%), and non-recovery in the other 12 (12.50%). The degree of OMNP at onset, SAH, and time from onset to treatment were significantly (P<0.05) correlated with the resolution of OMNP. Univariate analysis revealed that younger age of the patient, degree of OMNP at onset, presence of subarachnoid hemorrhage, and time from disease onset to treatment were significantly (P<0.05) associated with the recovery of OMNP. Multivariate analysis revealed that the younger age, degree of OMNP at onset, and time from disease onset to treatment were significantly (P<0.05) associated with the recovery of OMNP. CONCLUSION: Endovascular embolization of Pcom aneurysms concomitant with OMNP can effectively improve the OMNP symptoms, especially for patients with moderate and a shorter history of OMNP. Younger age, degree of oculomotor nerve palsy at onset, and time from onset to treatment may significantly affect recovery of oculomotor nerve palsy.

Exploration of clinical and ethical issues in an expanded newborn metabolic screening programme: a qualitative interview study of healthcare professionals in Hong Kong.

INTRODUCTION: The Newborn Screening Programme for Inborn Errors of Metabolism (NBSIEM) enables early intervention and prevents premature mortality. Residual dried bloodspots (rDBS) from the heel prick test are a valuable resource for research. However, there is minimal data regarding how stakeholders in Hong Kong view the retention and secondary use of rDBS. This study aimed to explore views of the NBSIEM and the factors associated with retention and secondary use of rDBS among healthcare professionals in Hong Kong. METHODS: Between August 2021 and January 2022, semi-structured interviews were conducted with 30 healthcare professionals in obstetrics, paediatrics, and chemical pathology. Key themes were identified through thematic analysis, including views towards the current NBSIEM and the retention and secondary use of rDBS. RESULTS: After implementation of the NBSIEM, participants observed fewer patients with acute decompensation due to undiagnosed inborn errors of metabolism. The most frequently cited clinical utilities were early detection and improved health outcomes. Barriers to rDBS storage and its secondary use included uncertain value and benefits, trust concerns, and consent issues. CONCLUSION: This study highlighted healthcare professionals' concerns about the NBSIEM and uncertainties regarding the handling or utilisation of rDBS. Policymakers should consider these concerns when establishing new guidelines.

[Exploration and validation of optimal cut-off values for tPSA and fPSA/tPSA screening of prostate cancer at different ages].

Objective: To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China. Methods: Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (＜60, 60-＜70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values. Results: A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening. Conclusion: To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.

[Study on liver tissue derived-extracellular vesicles regulating the osteogenic differentiation ability of mesenchymal stem cells and promoting the healing of jaw bone defects].

Objective: To explore the biological process of liver tissue-derived extracellular vesicle (LT-EV) in promoting osteogenic differentiation of mesenchymal stem cells and healing of jaw defects to provide a feasible treatment method for the clinical treatment of jaw bone defects. Methods: Enzymatic hydrolysis and differential centrifugation were used to extract LT-EV, scanning electron microscopy, Western blotting, and nanoparticle tracking analyzers were used to identify and characterize LT-EV, and further to explore the biological functions of LT-EV through proteomics and Kyoto Encyclopedia of Genes and Genomes. Flow cytometry was used to detect LT-EV plasma concentration and to calculate the plasma half-life of LT-EV. Small animal in vivo imaging system was used to detect the biological distribution of LT-EV 24 hours after injection. Six C57BL/6 mice were divided into control group and LT-EV group (3 mice in each group) by simple random sampling method. All mice underwent jaw bone defect surgery and tail vein injection every 7 days (the control group was injected with phosphoric buffer saline, LT-EV group was injected with LT-EV), micro-CT was used to evaluate the degree of mouse jaw bone healing 28 days after surgery, HE staining was used to analyze the multi-organ biosafety of LT-EV, and immunofluorescence staining was used to detect the jaw bone expression of osteogenic marker proteins in the defect area. Human jaw bone mesenchymal stem cells (hJBMSC) induced by osteogenic differentiation were treated with LT-EV (obtained from orthognathic surgery patients provided by the Department of Traumatology and Orthognathic Surgery of School of Stomatology of The Fourth Military Medical University resected normal jaw bone fragments), and the difference in osteogenic differentiation ability between the hJBMSC group and the control group (phosphate buffer saline treatment) was compared, and the in vitro bone differentiation promoting effect of LT-EV was verified through alkaline phosphatase (ALP) staining and real-time fluorescence quantitative PCR. Results: The yield of LT-EV was high, and proteomics and Kyoto Encyclopedia of Genes and Genomes showed that LT-EV contained a series of proteins that regulated cell biological functions. LT-EV injected into the tail vein could reach the mouse jaw bone defect area and promote the regeneration and repair of the jaw bone defect [the bone volume fractions of the LT-EV group and the control group were (36.06±4.20)% and (18.58±5.61)%, respectively; t=4.32, P=0.013], and had good biosafety. LT-EV could promote osteogenic differentiation of hJBMSC in vitro. Compared to the control group, ALP staining and osteogenic gene expression levels were significantly enhanced after osteogenic differentiation of hJBMSC (P<0.05). Conclusions: LT-EV exhibits a high yield, ease of acquisition, high biological safety, and excellent bone-promoting effects. It holds promise as a novel cell-free therapy strategy for regenerating craniofacial bone defects.

Joint inference of clonal structure using single-cell genome and transcriptome sequencing data.

Latest advancements in the high-throughput single-cell genome (scDNA) and transcriptome (scRNA) sequencing technologies enabled cell-resolved investigation of tissue clones. However, it remains challenging to cluster and couple single cells for heterogeneous scRNA and scDNA data generated from the same specimen. In this study, we present a computational framework called CCNMF, which employs a novel Coupled-Clone Non-negative Matrix Factorization technique to jointly infer clonal structure for matched scDNA and scRNA data. CCNMF couples multi-omics single cells by linking copy number and gene expression profiles through their general concordance. It successfully resolved the underlying coexisting clones with high correlations between the clonal genome and transcriptome from the same specimen. We validated that CCNMF can achieve high accuracy and robustness using both simulated benchmarks and real-world applications, including an ovarian cancer cell lines mixture, a gastric cancer cell line, and a primary gastric cancer. In summary, CCNMF provides a powerful tool for integrating multi-omics single-cell data, enabling simultaneous resolution of genomic and transcriptomic clonal architecture. This computational framework facilitates the understanding of how cellular gene expression changes in conjunction with clonal genome alternations, shedding light on the cellular genomic difference of subclones that contributes to tumor evolution.

[A clinical-radiomics nomogram for differentiating focal organizing pneumonia and lung adenocarcinoma].

OBJECTIVE: To evaluate the performance of a clinical-radiomics model for differentiating focal organizing pneumonia (FOP) and lung adenocarcinoma (LUAD). METHODS: We retrospectively analyzed the data of 60 patients with FOP confirmed by postoperative pathology at the First Medical Center of the Chinese PLA General Hospital from January, 2019 to December, 2022, who were matched with 120 LUAD patients using propensity score matching in a 1∶2 ratio. The independent risk factors for FOP were identified by logistic regression analysis of the patients' clinical data. The cohort was divided into a training set (144 patients) and a test set (36 patients) by random sampling. Python 3.7 was used for extracting 1835 features from CT image data of the patients. The radiographic features and clinical data were used to construct the model, whose performance was validated using ROC curves in both the training and test sets. The diagnostic efficacy of the model for FOP and LUAD was evaluated and a diagnostic nomogram was constructed. RESULTS: Statistical analysis revealed that an history of was an independent risk factor for FOP (P=0.016), which was correlated with none of the hematological findings (P > 0.05). Feature extraction and dimensionality reduction in radiomics yielded 30 significant labels for distinguishing the two diseases. The top 3 most discriminative radiomics labels were GraylevelNonUniformity, SizeZoneNonUniformity and shape-Sphericity. The clinical-radiomics model achieved an AUC of 0.909 (95% CI: 0.855-0.963) in the training set and 0.901 (95% CI: 0.803-0.999) in the test set. The model showed a sensitivity of 85.4%, a specificity of 83.5%, and an accuracy of 84.0% in the training set, as compared with 94.7%, 70.6%, and 83.3% in the test set, respectively. CONCLUSION: The clinical-radiomics nomogram model shows a good performance for differential diagnosis of FOP and LUAD and may help to minimize misdiagnosis-related overtreatment and improve the patients' outcomes.

[Surgical treatment and prognosis analysis of hilar cholangiocarcinoma].

Objective: To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma. Methods: This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of (M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) µmol/L(range: 5.4 to 722.8 µmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 µmol/L to 85.5 µmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results: Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ (P=0.009), hemi-hepatectomy and extended resection (P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1:OR=1.43 (0.61-3.35),P=0.413;T3 vs. T1:OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions: Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

[Interaction between implants and natural teeth in patients with severe periodontitis:a retrospective study].

Objective: To evaluate the clinical outcomes after implant restoration in the posterior region of severe periodontitis patients and to investigate the factors of natural tooth affecting the implant from the perspective of improving natural periodontal health, which may provide a reference for clinical practice. Methods: Fifty-three patients with severe periodontitis who visited the Department of Periodontology at the Affiliated Stomatological Hospital of China Medical University from June 2014 to June 2023 and completed posterior implant treatment with single crown were included, among which were 16 males and 37 females, aged (52.2±8.0) years old, with a total of 136 implants, 135 adjacent natural teeth in the edentulous area. We retrospectively compared the changes of probing depth (PD), bleeding on probing (BOP) and tooth mobility (TM) before and after implant placement. Besides, we explored the effects of the natural periodontal status on PD, BOP and marginal bone loss (MBL) of the implant at the last follow-up examination by univariate analysis and multivariate analysis. Results: Fifty-three patients were followed up for (44.5±14.1) months in average, with longest interval of (8.3±2.7) months. The PD of adjacent natural teeth in the edentulous area improved from 4.3 (3.6, 4.6) mm before implantation to 3.6 (3.2, 4.0) mm in the last review (P<0.01), while the proportion of BOP (+) improved from 69.6% (94/135) before implantation to 46.7% (63/135) in the last review (P<0.01). The proportion of teeth with mobility≥Ⅱ decreased from 15.6% (21/135) to 5.9% (8/135) (P<0.01). The percentage of natural teeth with PD≥4 mm in the same segment improved from 21.0% (13.3%, 26.0%) before implantation to 18.0% (12.0%, 25.0%) in the last review (P<0.05). The BOP (+)% improved from 29.0% (24.0%, 35.0%) before implantation to 23.0% (18.0%, 31.0%) in the last review (P<0.05), and the number of teeth with mobility≥Ⅱ decreased from 0.0 (0.0, 1.0) to 0.0 (0.0, 0.8) (P<0.05). The functional tooth unit score of full natural teeth increased from 8.0 (6.0, 10.0) points before implantation to 12.0 (12.0, 12.0) points in the last review (P<0.01). PD≥4 mm % increased from 11.0% (6.0%, 25.0%) before implantation to 13.0% (3.0%, 21.0%) in the last review (P<0.05) and there was no significant differences in BOP (+)% [(17.0±9.7) % vs (14.6±7.2) %, P>0.05]. The number of teeth with mobility≥Ⅱ decreased from 1.0 (0.0, 1.8) to 0.0 (0.0, 0.8) (P<0.05). Conclusions: Under the premise of regular supportive care, implant restorative treatment in the posterior region of severe periodontitis patients is helpful to improve the PD, BOP and TM of remaining natural teeth. Besides, the stages and grades of periodontitis at initial diagnosis can affect the PD and BOP of implants.

Machine learning framework develops neutrophil extracellular traps model for clinical outcome and immunotherapy response in lung adenocarcinoma.

Neutrophil extracellular traps (NETs) are novel inflammatory cell death in neutrophils. Emerging studies demonstrated NETs contributed to cancer progression and metastases in multiple ways. This study intends to provide a prognostic NETs signature and therapeutic target for lung adenocarcinoma (LUAD) patients. Consensus cluster analysis performed by 38 reported NET-related genes in TCGA-LUAD cohorts. Then, WGCNA network was conducted to investigate characteristics genes in clusters. Seven machine learning algorithms were assessed for training of the model, the optimal model was picked by C-index and 1-, 3-, 5-year ROC value. Then, we constructed a NETs signature to predict the overall survival of LUAD patients. Moreover, multi-omics validation was performed based on NETs signature. Finally, we constructed stable knockdown critical gene LUAD cell lines to verify biological functions of Phospholipid Scramblase 1 (PLSCR1) in vitro and in vivo. Two NETs-related clusters were identified in LUAD patients. Among them, C2 cluster was provided as "hot" tumor phenotype and exhibited a better prognosis. Then, WGCNA network identified 643 characteristic genes in C2 cluster. Then, Coxboost algorithm proved its optimal performance and provided a prognostic NETs signature. Multi-omics revealed that NETs signature was involved in an immunosuppressive microenvironment and predicted immunotherapy efficacy. In vitro and in vivo experiments demonstrated that knockdown of PLSCR1 inhibited tumor growth and EMT ability. Besides, cocultural assay indicated that the knockdown of PLSCR1 impaired the ability of neutrophils to generate NETs. Finally, tissue microarray (TMA) for LUAD patients verified the prognostic value of PLSCR1 expression. In this study, we focus on emerging hot topic NETs in LUAD. We provide a prognostic NETs signature and identify PLSCR1 with multiple roles in LUAD. This work can contribute to risk stratification and screen novel therapeutic targets for LUAD patients.

Enduring Consensus Guidelines for Cervical Cancer Screening and Management: Introduction to the Scope and Process.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines (Enduring Guidelines) effort is a standing committee to continuously evaluate new technologies and approaches to cervical cancer screening, management, and surveillance. METHODS AND RESULTS: The Enduring Guidelines process will selectively incorporate new technologies and approaches with adequate supportive data to more effectively improve cancer prevention for high-risk individuals and decrease unnecessary procedures in low-risk individuals. This manuscript describes the structure, process, and methods of the Enduring Guidelines effort. Using systematic literature reviews and primary data sources, risk of precancer will be estimated and recommendations will be made based on risk estimates in the context of established risk-based clinical action thresholds. The Enduring Guidelines process will consider health equity and health disparities by assuring inclusion of diverse populations in the evidence review and risk assessment and by developing recommendations that provide a choice of well-validated strategies that can be adapted to different settings. CONCLUSIONS: The Enduring Guidelines process will allow updating existing cervical cancer screening and management guidelines rapidly when new technologies are approved or new scientific evidence becomes available.

Recommendations for Use of p16/Ki67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results. METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. RESULTS: For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier. CONCLUSIONS: Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations.