[Long-term health-related quality of life and related factors in children with severe hemophilia A who received regular low-dose prophylaxiss].

Objective: To investigate long-term health-related quality of life (HRQoL) and related factors in children with severe hemophilia A (HA) who received regular low-dose prophylaxis. Methods: Clinical data of severe HA children who began to receive regular low-dose coagulation factor Ⅷ (FⅧ) prophylaxis in Peking Union Medical College Hospital from January 1, 2008 to December 31, 2011 were retrospectively enrolled. The longest last follow-up period was May 31, 2023. The attendance of school or work and daily physical activity during the last follow-up were investigated. The patients were divided into full attendance group and incomplete attendence group according to attendance. The patients were divided into into exercise attainment group (reached Chinese sports recommendation) and exercise nonattainment group according to the exercise status. Barthel score was used to assess activities of daily living and Haemo-QoL was used to assess quality of life. Long-term HRQoL for children aged 8-16 years and patients aged 17 years and above were assessed using Haemo-QoL SF and Haem-A-QoL versions, respectively. Spearman correlation analysis was used to examine the correlation between treatment conditions and Haemo-QoL scores. Results: A total of 22 cases were enrolled, the prophylaxis initiation age ranged from 1.8-17.9 (10.4±3.8) years old. The average prophylactic FⅧ dose during low-dose prophylaxis was 24.2 U/kg per week and the follow-up time was 6.3-15.1 (9.6±2.8) years. At the last follow-up, the age of the patients was (20.2±5.4) years, of which 14 (63.6%) were adults over 18 years old. There were 15 patients in the full attendance group and 7 patients in the incomplete attendence group. Compared with the full attendance group, the incomplete attendence group had a smaller preventive treatment dose [M(Q1, Q3), (28.4±11.1) vs (15.3±3.7) U/kg, P=0.012], shorter preventive treatment time [148. 1 (18.6, 346.5) vs 48.0 (32.0, 156.9) weeks, P=0.017], and higher annual joint bleeding rate (AJBR) [12.5 (6.0, 22.3) vs 14.2 (13.2, 17.8) times, P=0.017]. There were 7 cases in the exercise attainment group and 15 cases in the exercise nonattainment group. Compared to the exercise attainment group, the exercise nonattainment group had shorter preventive treatment time[313. 7 (156.9, 366.0) vs 48.0 (16.5, 108.9) weeks, P=0.006], a higher AJBR [7.0 (5.1, 10.0) vs 23.3 (12.5, 29.8), P=0.003] and a higher hemophilia joint health score (HJHS) [9.0 (2.0, 15.5) vs 23.0 (12.0, 27.8), P=0.014]. Barthel score showed 81.8% (18 cases) of the patients' living ability was not influenced by the illness. In Haemo-QoL score, the total score of Haemo-QoL SF in 7 cases was (47.6±17.0) scores, the total score of Haem-A-QoL in 15 cases was (45.2±22.6) scores. The daily activity dimension of the Haem-A-QoL score was the lowest [38.2 (10.9, 45.5) scores], which was positively correlated with the starting age of prophylactic initiation (r=0.501, P=0.057), and negatively correlated with the duration of prophylaxis (r=-0.545, P=0.036). Conclusions: Regular low-dose prophylaxis could improve the long-term HRQoL of some children with severe HA, and children with higher prophylactic doses and longer prophylactic treatment time have higher quality of life.

[Perceptions of transanal total mesorectal excision surgical quality and patient screening].

As a rapid developing rectal cancer procedure that has been in existence for more than a decade, transanal total mesorectal excision (taTME) has had a rough experience along the way, suggesting the importance of improving its surgical quality. In the current view of quality control of taTME, its main advantages are that it could increase the distance of distal margins, reduce the positive rate of circumferential margins, and improve the quality of total mesorectal excision. As few high-quality clinical studies have been conducted, the limitations brought about by confounding bias and publication bias that could not be excluded in current published studies call for a cautious interpretation of the current conclusions. At this stage taTME is only recommended in highly selective patients and centers. Under these circumstances, we aim to discuss the quality assessment of the taTME procedure and the selection of patients and centers. Based on current evidence and practical experience, we typically select patients with difficult pelvis, low rectal cancer, and/or those requiring direct visual recognition of the distal margin after neoadjuvant chemoradiation to perform taTME in our center.

[Effects of tumor location and mismatch repair on clinicopathological features and survival for non-metastatic colon cancer: A retrospective, single center, cohort study].

Objective: To analyze the differences in clinicopathological features of colon cancers and survival between patients with right- versus left-sided colon cancers. Methods: This was a retrospective cohort study. Information on patients with colon cancer from January 2016 to August 2020 was collected from the prospective registry database at Peking Union Medical College Hospital . Primary tumors located in the cecum, ascending colon, and proximal two-thirds of the transverse colon were defined as right-sided colon cancers (RCCs), whereas primary tumors located in the distal third of the transverse colon, descending colon, or sigmoid colon were defined as left-sided colon cancers (LCCs). Clinicopathological features were compared using the χ2 test or Mann-Whitney U test. Survival was estimated by Kaplan-Meier curves and the log-rank test. Factors that differed significantly between the two groups were identified by multivariate survival analyses performed with the Cox proportional hazards function. One propensity score matching was performed to eliminate the effects of confounding factors. Results: The study cohort comprised 856 patients, with TNM Stage I disease, 391 (45.7%) with Stage II, and 336 (39.3%) with Stage III, including 442 (51.6%) with LCC and 414 (48.4%) with RCC and 129 (15.1%). Defective mismatch repair (dMMR) was identified in 139 patients (16.2%). Compared with RCC, the proportion of men (274/442 [62.0%] vs. 224/414 [54.1%], χ2=5.462, P=0.019), body mass index (24.2 [21.9, 26.6] kg/m2 vs. 23.2 [21.3, 25.5] kg/m2, U=78,789.0, P<0.001), and well/moderately differentiated cancer (412/442 [93.2%] vs. 344/414 [83.1%], χ2=22.266, P<0.001) were higher in the LCC than the RCC group. In contrast, the proportion of dMMR (40/442 [9.0%] vs. 99/414 [23.9%], χ2=34.721, P<0.001) and combined vascular invasion (106/442[24.0%] vs. 125/414[30.2%], χ2=4.186, P=0.041) were lower in the LCC than RCC group. The median follow-up time for all patients was 48 (range 33, 59) months. The log-rank test revealed no significant differences in disease-free survival (DFS) (P=0.668) or overall survival (OS) (P=0.828) between patients with LCC versus RCC. Cox proportional hazards model showed that dMMR was significantly associated with a longer DFS (HR=0.419, 95%CI: 0.204‒0.862, P=0.018), whereas a higher proportion of T3-4 (HR=2.178, 95%CI: 1.089‒4.359, P=0.028), N+ (HR=2.126, 95%CI: 1.443‒3.133, P<0.001), and perineural invasion (HR=1.835, 95%CI: 1.115‒3.020, P=0.017) were associated with poor DFS. Tumor location was not associated with DFS or OS (all P>0.05). Subsequent analysis showed that RCC patients with dMMR had longer DFS than did RCC patients with pMMR (HR=0.338, 95%CI: 0.146‒0.786, P=0.012). However, the difference in OS between the two groups was not statistically significant (HR=0.340, 95%CI:0.103‒1.119, P=0.076). After propensity score matching for independent risk factors for DFS, the log-rank test revealed no significant differences in DFS (P=0.343) or OS (P=0.658) between patients with LCC versus RCC, whereas patient with dMMR had better DFS (P=0.047) and OS (P=0.040) than did patients with pMMR. Conclusions: Tumor location is associated with differences in clinicopathological features; however, this has no impact on survival. dMMR status is significantly associated with longer survival: this association may be stronger in RCC patients.

New Monomer Capable of Dual Chemical Binding with Dentin to Improve Bonding Durability.

The water-rich nature of the dentin bonding microenvironment, coupled with the stresses on the bonding interface, contributes to the hydrolytic degradation of the hybrid layer, resulting in a decline in bonding durability and, ultimately, restoration failure. Currently, the 3-step etch-and-rinse technique remains the gold standard for dentin bonding, and the bonding mechanism mainly involves a physical interaction with little chemical bonding. In this study, we have developed a siloxane-modified polyurethane monomer (SPU) with acrylate and siloxane modifications that chemically binds to both collagen and hydroxyapatite in dentin. Formulated as a bisphenol A-glycidyl methacrylate alternative, the SPU monomer-based adhesive was designed to improve dentin bonding quality and durability. Attenuated total reflection Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscope, and hydroxyproline release assays were performed on SPU-treated collagen, hydroxyapatite, and acid-etched dentin slices to dentin. The physicochemical properties of the configured SPU adhesives were profiled for polymerization behavior, water contact angle, and tensile strain and strength. The bonding effectiveness was assessed through micro-tensile strength, nano-leakage tests conducted on the bonded samples before and after thermal cycle aging. Finally, we further conducted in vivo and in vitro experiments to assess the biocompatibility of adhesives. The results showed that the siloxane groups of SPU monomer could covalently bind to dentin collagen and hydroxyapatite. The incorporation of SPU in the adhesive led to a significant increase in adhesive polymerization (P < 0.05) and tensile strain at break up to 134.11%. Furthermore, the SPU adhesive significantly improved dentin bond strength (P < 0.05), reduced interfacial nano-leakage (P < 0.05), and displayed good biocompatibility. In conclusion, the application of SPU, which achieves dual chemical bonding with dentin, can improve the quality of the hybrid layer, buffer the interfacial stresses, enhance the interfacial resistance to hydrolysis, and provide a feasible strategy to extend the service life of adhesive restorations.

[Association of sleep duration and physical exercise with dyslipidemia in older adults aged 80 years and over in China].

Objective: To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China. Methods: The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia. Results: The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% (HR=1.22, 95%CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% (HR=0.67, 95%CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion: Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.