Later-Life Cognitive Trajectories and Risk of Death: Results from a 6-Year Longitudinal Study of 7082 Chinese.

BACKGROUND AND OBJECTIVES: To identify cognitive decline trajectories in a Chinese elderly population, explore the associations between these trajectories and mortality, and further identify risk factors related to certain trajectories of cognitive decline. DESIGN: Prospective cohort study. SETTING: The group-based trajectory modeling and Cox proportional hazards models were conducted to explore the association between cognitive trajectory groups and mortality, while multinomial logistic regression models were constructed to estimate potential risk factors. PARTICIPANTS: We included 7082 participants aged 65 years or above in three consecutive but non-overlapping cohorts of the Chinese Longitudinal Healthy Longevity Survey with the Chinese version of the Mini-Mental State Examination up to 6 years. Participants were subsequently followed for a median (IQR) of 2.89 (1.38-3.12) years to obtain their survival status and date of death. MEASUREMENTS: Chinese version of the Mini-Mental State Examination was used to measure participants' cognitive function. RESULTS: Through use of group-based trajectory modeling, we determined three cognitive trajectory groups. Then, after adjusting for confounding factors, we found a monotonic and positive association between cognitive decline and mortality risk. Meanwhile, the association varied among elderly populations in different age groups and BMI categories, but did not differ by sex, smoking, drinking and exercising. Older seniors, females and those with poorer baseline cognitive function and less social participation tended to be more likely to be in the unfavorable trajectory groups. CONCLUSION: We found that the faster the cognitive decline, the higher the mortality, especially among those aged 65-79 years and those overweight. Our findings suggested the importance of implement better monitoring of the cognitive function of the elderly population.

[Clinicopathological study of 24 cases of monkeypox virus infection-related rashes].

Objective: To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests. Methods: Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope® hybridization and electron microscopy. Results: All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri's bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope® hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions: The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.

[A single-center study on the distribution and shifting trend of infectious keratitis pathogens from 2018 to 2022].

Objective: To investigate the pathogen species, composition, and distribution characteristics of infectious keratitis pathogens in Shandong Province and its surrounding areas. Methods: In this cross-sectional study, patients with keratitis who underwent corneal sampling and microbiological culture at the Shandong Eye Hospital from January 1, 2018 to December 31, 2022 were included. Under topical anesthesia, the edge of the lesion was scraped by an experienced physician. The samples were inoculated on blood agar and Sabouraud dextrose agar plates, separately for bacterial and fungal culture and identification. If necessary, the samples were inoculated on a non-nutrient agar medium with Escherichia coli for Acanthamoeba culture. Bacterial isolates were identified using Vitek 2 compact or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Fungal isolates were identified based on morphological characteristics or sent to a company for sequencing in cases of difficult identification. The epidemiological data of the patients, pathogen species and number (counting as 1 strain if the same strain was isolated from multiple corneal specimens of the same patient), culture positivity rate, and seasonal distribution were recorded. Differences in pathogen positivity rates among different seasons were analyzed using the chi-square test. Results: Among the 4, 024 patients with infectious keratitis during the study period, there were 2 510 males (62.3%) and 1 514 females (37.6%), aged from 46 days to 94 years. Positive microbial culture results were achieved in 2, 363 patients (58.7%), including 906 cases (38.3%) with bacterial positivity, 1 231 cases (52.1%) with fungal positivity, 28 cases (1.2%) with Acanthamoeba positivity, and 198 cases (8.4%) with mixed fungal and bacterial infections. A total of 2 561 strains were isolated, including 1 104 bacterial strains. The most common bacteria were coagulase-negative Staphylococcus spp. (623/1 104, 56.4%), followed by Streptococcus spp. (131/1 104, 11.9%) and Pseudomonas aeruginosa (68/1 104, 6.2%). The most common fungi were Fusarium spp. (634/1 429, 44.4%), followed by Aspergillus spp. (279/1 429, 19.5%) and Alternaria spp. (229/1 429, 16.0%). Bacterial keratitis was more common in summer and autumn, while fungal keratitis was more common in autumn and winter. Conclusions: Among infectious keratitis cases in Shandong Eye Hospital, Fusarium species were predominant fungal pathogens, while coagulase-negative Staphylococcus predominated in bacterial pathogens. Both fungal and bacterial corneal infections showed seasonal variations.

The prediction of treatment outcome in NSCLC patients harboring an EGFR exon 20 mutation using molecular modeling.

INTRODUCTION: The structural effect of uncommon heterogenous in-frame deletion and/or insertion mutations within exon 20 (EGFRex20+) in relation to therapy response is poorly understood. This study aims to elucidate the structural alterations caused by EGFRex20+ mutations and correlate these changes with patient responses. MATERIAL AND METHOD: We selected EGFRex20+ mutations from advanced NSCLC patients in the Position20 and AFACET studies for computational analysis. Homology models representing both inactive and active conformations of these mutations were generated using the Swiss-Model server. Molecular docking studies with EGFR-TKIs was conducted using smina, followed by Molecular Dynamic (MD) simulations performed with GROMACS. These computational findings were compared with clinical outcomes to evaluate their potential in predicting patient response. RESULTS: Our docking studies of 29 EGFRex20+ mutations revealed that the binding energies of afatinib, osimertinib, zipalertinib, and sunvozertinib, compared to the wild type, do not significantly impact either TKI's efficacy. MD simulations for eight EGFRex20+ mutations (A763_Y764insFQEA, A767_V769dup, S768_D770dup, D770_N771insG, D770_P772dup, N771_H773dup, H773_V774insY and H773_V774delinsLM) revealed varying degrees of instability. For six variants, predicted activation based on the αC-helix stability and orientation, as well as TKI sensitivity, aligned well with clinical observations from the Position20 and AFACET studies. Two mutations (D770_N771insG and N771_H773dup) predicted as poor to moderate responders, showed minimal activation of the αC-helix region, warranting further investigation. CONCLUSION: In conclusion, MD simulations can effectively predict patient outcomes by connecting computational results with clinical data and advancing our understanding of EGFR mutations and their therapeutic responses.

SERUM CALCIUM WAS NEGATIVELY ASSOCIATED WITH SERUM IRON AMONG GENERAL POPULATION: FINDINGS FROM A CROSS-SECTION STUDY.

INTRODUCTION: The progression of ferroptosis has been found to be associated with the onset and progression of many diseases. Disruption of iron homeostasis can lead to ferroptosis. We had previously hypothesized that vitamin D may affect serum calcium levels, which in turn regulates ferroptosis by regulating serum iron levels. However, the relationship between serum calcium level and serum iron level is unclear. The purpose of our study was to explore the relationship between serum calcium level and serum iron level among general population in Taizhou, China. METHODS: In this study, a cross-sectional study was conducted. Serum calcium levels and serum iron levels were determined in our work. Pearson's correlation analysis was used to determine the association between serum calcium level and serum iron level. RESULTS: The results showed that serum iron level was negatively correlated with serum calcium level and age. After controlling for age, sex and marital status, serum iron level was still negatively correlated with serum calcium level. CONCLUSIONS: The results suggest that improving serum calcium levels may be a potential strategy for regulating iron metabolism homeostasis. Whether calcium supplementation can reduce serum iron levels in people with low serum calcium levels needs further investigation.

Steady-state properties of multi-orbital systems using quantum Monte Carlo.

A precise dynamical characterization of quantum impurity models with multiple interacting orbitals is challenging. In quantum Monte Carlo methods, this is embodied by sign problems. A dynamical sign problem makes it exponentially difficult to simulate long times. A multi-orbital sign problem generally results in a prohibitive computational cost for systems with multiple impurity degrees of freedom even in static equilibrium calculations. Here, we present a numerically exact inchworm method that simultaneously alleviates both sign problems, enabling simulation of multi-orbital systems directly in the equilibrium or nonequilibrium steady-state. The method combines ideas from the recently developed steady-state inchworm Monte Carlo framework [Erpenbeck et al., Phys. Rev. Lett. 130, 186301 (2023)] with other ideas from the equilibrium multi-orbital inchworm algorithm [Eidelstein et al., Phys. Rev. Lett. 124, 206405 (2020)]. We verify our method by comparison with analytical limits and numerical results from previous methods.

Compensatory changes after spinal cord injury in a remyelination deficient mouse model.

The development of therapeutic strategies to reduce impairments following spinal cord injury (SCI) motivates an active area of research, because there are no effective therapies. One strategy is to address injury-induced demyelination of spared axons by promoting endogenous or exogenous remyelination. However, previously, we showed that new myelin was not necessary to regain hindlimb stepping following moderate thoracic spinal cord contusion in 3-month-old mice. The present analysis investigated two potential mechanisms by which animals can re-establish locomotion in the absence of remyelination: compensation through intact white matter and conduction through spared axons. We induced a severe contusion injury to reduce the spared white matter rim in the remyelination deficient model, with no differences in recovery between remyelination deficient animals and injured littermate controls. We investigated the nodal properties of the axons at the lesion and found that in the remyelination deficient model, axons express the Nav1.2 voltage-gated sodium channel, a sub-type not typically expressed at mature nodes of Ranvier. In a moderate contusion injury, conduction velocities through the lesions of remyelination deficient animals were similar to those in animals with the capacity to remyelinate after injury. Detailed gait analysis and kinematics reveal subtle differences between remyelination deficient animals and remyelination competent controls, but no worse deficits. It is possible that upregulation of Nav1.2 channels may contribute to establishing conduction through the lesion. This conduction could contribute to compensation and regained motor function in mouse models of SCI. Such compensatory mechanism may have implications for interpreting efficacy results for remyelinating interventions in mice and the development of therapies for improving recovery following SCI.

[Qingshen Granules alleviates renal fibrosis in mice by regulating exosomes, miR-330-3p, and CREBBP expression].

OBJECTIVE: To explore the effects of Qingshen Granules (QSG) on adenine-induced renal fibrosis in mice and in uric acid (UA)-stimulated NRK-49F cells and its mechanism for regulating exosomes, miR-330-3p and CREBBP. METHODS: A mouse model of adenine-induced renal fibrosis were treated daily with QSG at 8.0 g·kg-1·d-1 via gavage for 12 weeks. An adenoassociated virus vector was injected into the tail vein, and renal tissues of the mice were collected for analyzing exosomal marker proteins CD9, Hsp70, and TSG101 and expressions of Col-III, α-SMA, FN, and E-cad using Western blotting and immunofluorescence and for observing pathological changes using HE and Masson staining. In the cell experiment, NRK-49F cells were stimulated with uric acid (400 µmol/L) followed by treatment with QSG-medicated serum from SD rats, and the changes in expressions of the exosomal markers and Col-III, α-SMA, FN, and E-cad were analyzed. Dual luciferase reporter assay was employed to examine the targeting relationship between miR-330-3p and CREBBP, whose expressions were detected by RT-qPCR and Western blotting in treated NRK-49F cells. RESULTS: The mouse models of adenine-induced renal fibrosis showed significantly increased levels of CD9, Hsp70, and TSG101, which were decreased by treatment with QSG. The expressions of Col-III, α-SMA, and FN increased and Ecad decreased in the mouse models but these changes were reversed by QSG treatment. QSG treatment obviously alleviated renal fibrosis in the mouse models. Intravenous injection of adeno-associated viral vector obviously inhibited miR-330-3p, increased CREBBP levels, and reduced fibrosis in the mouse models. Dual luciferase assay confirmed CREBBP as a target of miR-330-3p, which was consistent with the results of the cell experiments. CONCLUSION: QSG inhibits renal fibrosis in mice by regulating the exosomes, reducing miR-330-3p levels, and increasing CREBBP expression.

[Pharmacodynamics of Qingxin Jieyu Granules for treatment of atherosclerosis and its regulatory mechanism for lipid metabolism].

OBJECTIVE: To elucidate the therapeutic mechanism of Qingxin Jieyu Granule (QXJYG) against atherosclerosis (AS) based on network pharmacology. METHODS: The major targets and pathways of QXJYG against AS were analyzed using network pharmacology. Rat models of AS established by high-fat feeding combined with intraperitoneal vitamin D3 injection were treated daily with normal saline, atorvastatin (13.15 mg/kg), or QXJYG at 0.99, 1.98, and 3.96 g/kg for 8 weeks (n=6). Ultrasound and HE staining were used to assess the function and pathologies of the abdominal aorta. Blood lipids and serum levels of Ang Ⅱ, ET-1, TXA2, PGI2, and ox-LDL of the rats were detected using an automatic biochemical analyzer or ELISA. The expressions of LOX-1, PPARγ, RXRα, p-P65, VCAM-1 and ICAM-1 in the abdominal aorta were detected with immunohistochemistry. RESULTS: The rat models of AS showed obvious abdominal aorta wall thickening, increased pulse wave velocity and pulse index, decreased inner diameter of the abdominal aorta, elevated levels of TC, LDL-C, Ang Ⅱ, ET-1 and TXA2, and lowered levels of HDL-C and PGI2. QXJYG and atorvastatin treatment of the rat models significantly alleviated histopathological changes of the abdominal aorta, decreased serum levels of TC, LDL-C, Ang Ⅱ, ET-1 and TXA2, and increased the levels of HDL-C and PGI2. Network pharmacology study suggested the therapeutic effect of QXJYG against AS was mediated by regulating lipid metabolism, PPAR and NF-κB pathways. Consistently, treatments with QXJYG were found to significantly decrease ox-LDL level and LOX-1, P-P65, VCAM-1 and ICAM-1 protein expressions while increasing PPARγ and RXRα expressions in the aorta of AS rats. CONCLUSION: QXJYG alleviates lipid metabolism disorder and improves histopathological changes of the abdominal aorta of AS rats possibly by lowering ox-LDL level, reducing LOX-1 expression, activating PPARγ and RXRα, and inhibiting P65 phosphorylation to reduce VCAM-1 and ICAM-1 expression in the aorta.

[Protective effect of Lonicerae japonicae flos extract against doxorubicin-induced liver injury in mice].

OBJECTIVE: To explore the mechanism underlying the protective effect of Lonicerae japonicae flos (LJF) extract against doxorubicin (DOX) -induced liver injury in mice. METHODS: Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets, based on which the protein-protein interaction (PPI) network was constructed using STRING database for screening the core targets using Cytoscape software. DAVID database was used for bioinformatics analysis, and the core components and core targets were verified using molecular docking study. In a mouse model of DOX-induced liver injury, the effect of LJF extract on liver pathologies, serum levels of ALT and AST, and hepatic expressions of HYP, ROS, TNF-α, IL-6, COL-Ⅳ and P53 proteins were evaluated using HE and Masson staining, ELISA, and Western blotting. RESULTS: We identified 12 core targets from 43 intersection genes involving cancer pathway, IL-17 signaling pathway, and TNF signaling pathways. Molecular docking study suggested that 10 core components of LJF could bind to different core targets. The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis, increased ROS content, and enhanced expressions of TNF-α, IL-6, HYP, COL-Ⅳ and P53 proteins in the liver tissue. All these changes in the mouse models were significantly alleviated by treatment with LJF extract, suggesting obviously lowered levels of oxidative stress, inflammation and fibrosis in the liver tissues. CONCLUSION: LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53, TNF and IL-6 to reduce liver oxidative stress, inflammation and fibrosis.

Enhancing trainee performance in obstetric ultrasound through an artificial intelligence system: randomized controlled trial.

OBJECTIVE: Performing obstetric ultrasound scans is challenging for inexperienced operators; therefore, the prenatal screening artificial intelligence system (PSAIS) software was developed to provide real-time feedback and guidance for trainees during their scanning procedures. The aim of this study was to investigate the potential benefits of utilizing such an artificial intelligence system to enhance the efficiency of obstetric ultrasound training in acquiring and interpreting standard basic views. METHODS: A prospective, single-center randomized controlled study was conducted at The First Affiliated Hospital of Sun Yat-sen University. From September 2022 to April 2023, residents with no prior obstetric ultrasound experience were recruited and assigned randomly to either a PSAIS-assisted training group or a conventional training group. Each trainee underwent a four-cycle practical scan training program, performing 20 scans in each cycle on pregnant volunteers at 18-32 gestational weeks, focusing on acquiring and interpreting standard basic views. At the end of each cycle, a test scan evaluated trainees' ability to obtain standard ultrasound views without PSAIS assistance, and image quality was rated by both the trainees themselves and an expert (in a blinded manner). The primary outcome was the number of training cycles required for each trainee to meet a certain standard of proficiency (i.e. end-of-cycle test scored by the expert at ≥ 80%). Secondary outcomes included the expert ratings of the image quality in each trainee's end-of-cycle test and the discordance between ratings by trainees and the expert. RESULTS: In total, 32 residents and 1809 pregnant women (2720 scans) were recruited for the study. The PSAIS-assisted trainee group required significantly fewer training cycles compared with the non-PSAIS-assisted group to meet quality requirements (P = 0.037). Based on the expert ratings of image quality, the PSAIS-assisted training group exhibited superior ability in acquiring standard imaging views compared with the conventional training group in the third (P = 0.012) and fourth (P < 0.001) cycles. In both groups, the discordance between trainees' ratings of the quality of their own images and the expert's ratings decreased with increasing training time. A statistically significant difference in overall trainee-expert rating discordance between the two groups emerged at the end of the first training cycle and remained at every cycle thereafter (P < 0.013). CONCLUSION: By assisting inexperienced trainees in obtaining and interpreting standard basic obstetric scanning views, the use of artificial intelligence-assisted systems has the potential to improve training effectiveness. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

The impact of mepolizumab on sleep impairment in CRSwNP: post hoc analyses of SYNAPSE and MUSCA.

BACKGROUND: The impact of mepolizumab on impaired sleep, one of the most bothersome symptoms in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), is unknown. This study aimed to determine the effect of mepolizumab and impact of comorbid upper and lower airway disease and blood eosinophil count (BEC) on sleep-/fatigue-related outcomes in CRSwNP. METHODS: This was an analysis of the Phase III SYNAPSE and MUSCA (NCT03085797/NCT02281318) trials of mepolizumab in patients with severe CRSwNP and severe asthma, respectively. Endpoints included change from baseline in 22-item Sino-Nasal Outcome Test (SNOT-22) sleep and fatigue domains (SYNAPSE: Weeks 24 and 52; MUSCA: Week 24) in the overall populations and post hoc subgroups (SYNAPSE: comorbid asthma, comorbid non-steroidal anti-inflammatory drug-exacerbated respiratory disease [N-ERD] and BEC; MUSCA: comorbid CRSwNP). RESULTS: In SYNAPSE, 289/407 patients with severe CRSwNP had comorbid asthma, 108 had N-ERD, and 278 had BEC ≥300 cells/µL. In MUSCA, 105/551 patients with severe asthma had comorbid CRSwNP. Baseline sleep and fatigue scores were worse in patients with comorbid airway disease and higher BEC. Improvements from baseline in sleep and fatigue scores were greater with mepolizumab versus placebo at Week 52 in SYNAPSE (difference in least squares mean change: -2.7 [sleep], -3.4 [fatigue], and Week 24 in SYNAPSE (-1.6 and -2.2) and MUSCA (-0.8 and -1.2), with consistent results across comorbidity and BEC subgroups. CONCLUSION: Mepolizumab improves sleep and fatigue in severe CRSwNP, irrespective of comorbid airway disease and BEC, with consistent effects in severe asthma with and without comorbid CRSwNP.

Metabolomics and amino acid profiling of plasma reveals the metabolite profiles associated with nitrogen utilisation efficiency in primiparous dairy cows.

Nitrogen (N) utilisation efficiency (NUE, milk N yield [g/d]/N intake [g/d]) is an important performance indicator in dairy farming. Determining the NUE-associated blood metabolite profile will contribute to the optimisation of nutritional strategies to further improve NUE among dairy cows. Here, 20 primiparous lactating cows with days in milk ranging from 95 to 115 days were selected from a total of 1 221 cows. Each cow's N intake and milk N yield were measured for 7 days. Subsequently, blood samples were collected before morning feeding. Based on analysis and calculations, cows were retrospectively classified into two groups based on their NUE values, namely, a low NUE group (LNUE, NUE = 24.8 ± 1.6%, n = 10, mean ± SD) and a high NUE group (HNUE, NUE = 35.2 ± 1.7%, n = 10, mean ± SD). Plasma samples were selected from six cows in each group for metabolomics and amino acid profiling. Among the 41 differential metabolites (DMs) identified in the metabolomic analysis, sucrose, MG(0:0/22:1(13Z)/0:0), 2-amino-6-hydroxyhexanoic acid, and L-glutamine exhibited significant correlations with NUE, milk yield, and BW (P < 0.05). Moreover, the five differential amino acids and amino acid metabolites (DAAs) identified in the amino acid profiling and 5 of the 6 differential amino acids and amino acid conjugates identified by plasma metabolomics were found to be less abundant in the HNUE group (P < 0.05). Specifically, there was a 39.4% decrease in L-arginine content and a 29.2% decrease in L-glutamine content (P < 0.05). Pathway analysis indicated that the DMs and DAAs were mainly involved in arginine biosynthesis, glutathione metabolism, arginine and proline metabolism, and tryptophan metabolism (pathway impact > 0.1). These results provided new insights into the new blood metabolite profile associated with NUE in dairy cows. These new insights can provide foundational information for the formulation of new strategies to further enhance NUE in dairy cows.

[Safety and efficacy analysis of a varicose vein sealant kit in the treatment of great saphenous vein dysfunction].

Objective: To investigate the safety and efficacy of a varicose vein sealant kit in the treatment of great saphenous vein dysfunction. Methods: It was a randomized controlled trial. A total of 180 patients with great saphenous vein dysfunction were enrolled prospectively, and scheduled for surgical treatment in 9 hospitals, including the Second Affiliated Hospital of Naval Medical University, Shanghai Oriental Hospital Affiliated to Tongji University, Xuanwu Hospital Capital Medical University, the First Hospital of Hebei Medical University, Ganzhou People's Hospital, Shanxi Bethune Hospital, the Second Affiliated Hospital of Zhejiang University School of Medicine, the Fourth Affiliated Hospital of Zhejiang University School of Medicine, and Zhongshan Hospital Affiliated to Xiamen University, from June to October 2022. Using a random number table method, the subjects were divided into an experimental group and a control group, with 90 cases in each group. The patients of experimental group received treatment with varicose vein sealant kit, while the patients of control group received radiofrequency ablation. The main outcome measure was the complete closure rate of the great saphenous vein in both groups of patients 3 months after surgery. The secondary outcome measures were the complete closure rate of the great saphenous vein in both groups of patients immediately after surgery and 6 months after surgery, the operation time for closing the main trunk of the great saphenous vein, pain score, venous clinical severity score (VCSS), Aberdeen varicose veins questionnaire (AVVQ) at different times before and after surgery, and the incidence of complications in both groups of patients. The non inferiority threshold for the two treatment methods is set at "-10.00%". Results: A total of 177 patients were ultimately enrolled. There were 89 cases in the experimental group, including 38 males and 51 females, with a median age [M (Q1, Q3)] of 59.7(49.6, 66.7) years, and 88 cases in the control group, including 30 males and 58 females, with a median age of 57.2(46.9, 65.9) years. A total of 174 patients completed a 3-month follow-up, and 167 patients completed a 6-month follow-up. The closure time of the main saphenous vein in the experimental group was (22.1±11.1) min, which was longer than the control group, which was (18.7±9.8) min (P=0.031). The complete closure rate of the great saphenous vein immediately after surgery in both the experimental group and the control group was 100%. The complete closure rates of the great saphenous vein at 3 months after surgery were 98.8% (85/86) and 98.9% (87/88), respectively. The lower limit of the 95%CI for the difference between the two groups was -3.19%, which was greater than the non-inferiority threshold of -10.00% (non-inferiority P<0.001). The complete closure rates of the great saphenous vein at 6 months after surgery were 97.6% (81/83) and 100% (84/84), the lower limit of the 95%CI for the difference between the two groups was -5.71%, which was greater than the non-inferiority threshold of -10.00% (non-inferiority P<0.001). The immediate pain scores after complete anesthesia awakening of the experimental group and the control group were both 1.0 (0, 2.0), with no statistically significant difference (P=0.365). The incidence of bruising in the experimental group and the control group one week after surgery was 61.2% (52/85) and 67.1% (57/85), respectively, with no statistically significant difference (P=0.181). There was no statistically significant difference in VCSS and AVVQ scores between groups before surgery and at 1, 3, and 6 months after surgery (all P>0.05). There was no statistically significant difference in the incidence of complications such as deep vein thrombosis, phlebitis, pain, and subcutaneous hematoma in the lower limbs 3 months after surgery (all P>0.05). Conclusion: The varicose vein sealant kit is safe and effective in treating great saphenous vein dysfunction, and can achieve a complete closure rate of great saphenous vein that is not inferior to traditional radiofrequency ablation.

[Clinical characteristics of appendix orifice polyps and the effect endoscopic super minimally invasive treatment].

To analyze the clinical characteristics of appendiceal orifice polyps and the effect of endoscopic super minimally invasive treatment. A retrospective analysis was conducted on the general situation (age and sex), the classification of appendiceal orifice polyps, the treatment method under endoscope, postoperative pathology and postoperative complications in patients who underwent resection of appendiceal orifice polyps at the Peking University First Hospital and the First Medical Center of the PLA General Hospital from January 1, 2022, to December 31, 2023. A total of 47 patients were included, consisting of 28 males and 19 females, with 35-86 (61±12) years. Appendiceal orifice polyps were classified into four types: type 0 (14 cases), type 1 (15 cases), type 2 (12 cases), and type 3 (6 cases). Among the endoscopic morphologies, 22 cases were granular laterally spreading tumors. Endoscopic mucosal dissection was performed in 37 cases. Postoperative appendiceal stent placement was performed in 1 case. The pathological types of polyps included adenoma in 15 cases, high-grade intraepithelial neoplasia in 10 cases, intramucosal carcinoma in 4 cases, submucosal carcinoma in 5 cases, inflammatory polyps in 1 cases, and sessile serrated lesion in 12 cases. Curative resection was performed in 44 cases. There were no postoperative complications such as bleeding, perforation, or acute appendicitis. The pathology of appendiceal polyps is mostly precancerous lesions, and the treatment scheme of endoscopic super minimally invasive resection is both safe and effective.

[A multicenter study on effect of delayed chemotherapy on prognosis of Burkitt lymphoma in children].

Objective: To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis. Methods: Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups. Results: Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old (OR=0.54,95%CI 0.30-0.93), tumor lysis syndrome before chemotherapy (OR=0.48,95%CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy (OR=0.55,95%CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions: The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

[Analysis of predictive effect of European treatment and outcome study long term survival score on survival outcomes in children with chronic myeloid leukemia of chronic phase].

Objective: To explore the predictive effect of European treatment and outcome study long term survival (ELTS) score on survival outcomes in chronic myeloid leukemia of chronic phase (CML-CP) children. Methods: A single-center retrospective cohort study was conducted. Clinical data of 216 children with CML-CP in Peking University People's Hospital from January 2010 to December 2023 were analyzed. Children were divided into low, intermediate and high-risk groups according to ELTS score. The survival outcomes and prognostic factors were analyzed. Kaplan-Meier method and Log-Rank test were used for survival analysis.Cox regression model was applied for analysis of prognostic factors. Results: Among the 216 children with CML-CP, there were 122 males and 94 females, with the diagnosis age of 11.0 (8.0, 14.7) years. The follow-up time was 77 (57, 99) months. According to ELTS score, 145, 52, and 19 children were classified as low, intermediate and high-risk group. For the low-risk and intermediate/high-risk groups, the 6-year failure-free survival (FFS) rates were (83.0±3.1)% and (64.6±5.7)%, the 6-year progression-free survival (PFS) rates were (91.4±2.3)% and (78.7±4.8)%, and the 6-year event-free survival (EFS) rates were (80.8±3.3)% and (64.2±5.7)%, with statistically significant difference (χ2=9.45, 7.16, 7.40, P=0.002, 0.007, 0.007), respectively.The 6-year overall survival (OS) rates were (98.5±1.0)% and (95.6±2.4)%, without statistically significant difference (χ2=0.35, P=0.550). Multivariate analysis showed that ELTS score was an independent prognostic factor or tendency for FFS (HR=1.97, 95%CI 1.11-3.49), PFS (HR=2.95, 95%CI 1.18-7.39), and no independent prognostic factor for EFS and OS were found. Conclusions: ELTS score at diagnosis can help stratify the risk of children with CML-CP. The children in intermediate/high-risk group are more likely to have treatment failure, disease progression than those in low-risk group, but the predictive ability of ELTS score for OS is limited.