ObjectiveThis study aims to explore the potential of different orders of magnitude single-nucleotide polymorphism (SNP) locus combinations for predicting distant kinship relationships. A high-density SNP locus set was constructed, and a comprehensive assessment of its inference capability was conducted. MethodsFirstly, we selected three commercial chip panels, CGA (Chinese genotyping array, Illumina), GSA (Global screening array, Illumina), Affy (23MF_V2 high-density SNP array, Affymetrix) and merged them after quality control, forming a high-density SNP locus panel(1 180 k). Secondly, we selected 161 samples and collected their peripheral blood samples by using whole-genome sequencing technology. Within this sample population, the levels of kinship relationships fully covered the range from level 1 to level 9, and the number of kinship pairs at each level was consistently maintained at over 50 pairs. From 161 samples data of whole-genome sequencing, the 1 180 k locus set was extracted, which is referred to as the high-density SNP locus set in the following text. The kinship inference was conducted using the identity-by-descent (IBD) algorithm with the selected optimal parameters. To comprehensively evaluate the performance of the high-density SNP locus set in kinship inference, we compared it with the three commercial chip panels, the intersection of these three chip loci, and the control sets constructed by randomly reducing the number of the high-density SNP locus set. Based on the changes in the IBD lengths, as well as the dynamic trends in prediction accuracy, we conducted a scientific assessment of the kinship inference capability of the high-density SNP locus set. ResultsAfter screening, a set of 1 184 334 autosomal SNPs was obtained. During the process of screening the optimal IBD length threshold, the result revealed that 0 cM, 1 cM, and 2 cM all demonstrated good applicability. However, to avoid the issue of a large amount of redundant information caused by setting a too low IBD length threshold, this study ultimately selected 2 cM as the optimal threshold. Compared with the average results of three chip panels, the high-density SNP locus set increased the total IBD length and the average IBD length across levels 1-9; the accuracy of the confidence interval for level 8 was 70.97%, which represented a 3.50% improvement; the average confidence interval accuracy for levels 1-8 was 91.39%, representing a 1.00% increase; and the false negative rates at levels 8 and 9 were reduced by 2.42% and 6.76%, respectively. The system efficacy of the high-density SNP locus set for kinship inference of first to eighth degree relationships reached 98.91%. Through random reduction of the high-density SNP locus set results, it is found that increasing the number of SNPs with the panel, the detection efficiency of IBD length showed a significant upward trend. At the same time, the overall trend in the accuracy of kinship relationship prediction as well as the confidence interval accuracy also indicated that both metrics steadily increased with the addition of more loci. ConclusionThe results show that the high-density SNPs panel significantly enhances the efficacy of distant kinship inference, accurately covering kinship degrees, with the average confidence interval accuracy for first to eighth degree relationships stably above 90%. The study finds that increasing the number of SNPs panel can improve the ability to predict distant kinship.

Background Nitrosamines (NAms), emerging as disinfection by-products in drinking water, are highly carcinogenic. Given the significant NAms contamination reported in various regions of China, evaluating the contamination levels and health risks of NAms in terminal direct drinking water is of great urgency. Objective To investigate the concentration levels of NAms in piped direct drinking water at primary and secondary schools in Shanghai, and to assess the potential health risks posed to different age groups through this exposure pathway. Methods A total of 198 water samples were collected from 66 primary and secondary schools across five districts in Shanghai from May to June 2023. The mass concentrations of eight major NAms were quantified using solid-phase extraction coupled with gas chromatography-mass spectrometry (GC-MS). A carcinogenic health risk model was employed to evaluate the lifetime cancer risks associated with NAms exposure via direct drinking water for various age groups. Results Among the 198 samples, NAms were detected in 196 samples, with concentrationsranging from below the limit of detection (LOD) to 106.06 ng·L⁻¹. The average concentration of total NAms was 21.30 ng·L⁻¹, with N-nitrosodimethylamine (NDMA) exhibiting the highest detection rate at 98.5%. Significant differences in NAms concentrations were observed among water treatment systems utilizing ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO) as core processes (P<0.05). The lifetime cancer risks for different age groups ranged from 1.38×10⁻⁶ to 1.11×10⁻⁵, with NDMA contributing the most to the overall risk (82.1%). The carcinogenic risk for adults (1.08×10⁻⁵) was higher than that for children and adolescents (1.38×10⁻⁶ to 2.61×10⁻⁶). Among children and adolescents under 18 years of age, the risk decreased as age increased. Conclusion Trace levels of NAms, primarily NDMA, are detected in the piped direct drinking water at primary and secondary schools in Shanghai, with concentrations vary significantly depending on the water treatment process. The carcinogenic risks of NAms exposure via direct drinking water for all age groups are below the acceptable level (1×10⁻⁴) recommended by the U.S. Environmental Protection Agency (EPA).

Background Nitrosamines (NAms), emerging as disinfection by-products in drinking water, are highly carcinogenic. Given the significant NAms contamination reported in various regions of China, evaluating the contamination levels and health risks of NAms in terminal direct drinking water is of great urgency. Objective To investigate the concentration levels of NAms in piped direct drinking water at primary and secondary schools in Shanghai, and to assess the potential health risks posed to different age groups through this exposure pathway. Methods A total of 198 water samples were collected from 66 primary and secondary schools across five districts in Shanghai from May to June 2023. The mass concentrations of eight major NAms were quantified using solid-phase extraction coupled with gas chromatography-mass spectrometry (GC-MS). A carcinogenic health risk model was employed to evaluate the lifetime cancer risks associated with NAms exposure via direct drinking water for various age groups. Results Among the 198 samples, NAms were detected in 196 samples, with concentrationsranging from below the limit of detection (LOD) to 106.06 ng·L⁻¹. The average concentration of total NAms was 21.30 ng·L⁻¹, with N-nitrosodimethylamine (NDMA) exhibiting the highest detection rate at 98.5%. Significant differences in NAms concentrations were observed among water treatment systems utilizing ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO) as core processes (P<0.05). The lifetime cancer risks for different age groups ranged from 1.38×10⁻⁶ to 1.11×10⁻⁵, with NDMA contributing the most to the overall risk (82.1%). The carcinogenic risk for adults (1.08×10⁻⁵) was higher than that for children and adolescents (1.38×10⁻⁶ to 2.61×10⁻⁶). Among children and adolescents under 18 years of age, the risk decreased as age increased. Conclusion Trace levels of NAms, primarily NDMA, are detected in the piped direct drinking water at primary and secondary schools in Shanghai, with concentrations vary significantly depending on the water treatment process. The carcinogenic risks of NAms exposure via direct drinking water for all age groups are below the acceptable level (1×10⁻⁴) recommended by the U.S. Environmental Protection Agency (EPA).

Purpose: The optimal sequencing of targeted therapies and the role of primary tumor resection (PTR) in KRAS wild-type metastatic colorectal cancer (mCRC) remain unclear. This study compared survival outcomes in patients treated with first-line cetuximab plus FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) versus bevacizumab plus FOLFIRI, followed by second-line oxaliplatin-based chemotherapy and later-line trifluridine/tipiracil or regorafenib. Methods: This retrospective cohort study used Taiwan’s National Health Insurance Research Database and the Taiwan Cancer Registry. Patients diagnosed with mCRC between 2013 and 2019 were included if they received first-line cetuximab or bevacizumab plus FOLFIRI, followed by later-line trifluridine/tipiracil or regorafenib. Patients were stratified by PTR status. Primary endpoints were overall survival and survival during trifluridine/tipiracil or regorafenib treatment. Secondary endpoints included time to treatment discontinuation (TTD) and TTD during trifluridine/tipiracil or regorafenib therapy. Stabilized inverse probability of treatment weighting was used for adjustment. Results: Among 559 patients, 278 were assigned to the non-PTR group and 281 to the PTR group. In the non-PTR group, the cetuximab cohort demonstrated significantly longer survival during trifluridine/tipiracil or regorafenib therapy (6.2 months vs. 4.9 months; hazard ratio [HR], 0.72) and longer TTD1 (the interval between initiation of first-line therapy and the start of second-line chemotherapy; 11.8 months vs. 9.5 months; HR, 0.67) than the bevacizumab cohort. Survival differences between regimens were less pronounced among patients who underwent PTR. Conclusion First-line cetuximab plus FOLFIRI may confer a survival advantage over bevacizumab in patients with KRAS wild-type mCRC without PTR, including during later-line therapy with trifluridine/tipiracil or regorafenib, whereas bevacizumab appears to provide more consistent benefits in those with PTR.

Objectives: . Idiopathic sudden sensorineural hearing loss (ISSNHL) is a significant cause of hearing loss. Intratympanic steroid injection (ITSI) is commonly used as an initial or salvage treatment; however, the lack of a standardized treatment protocol has resulted in variability in clinical practice. In addition, no efficient prediction model currently exists to support personalized management. Therefore, this study aimed to develop tailored management strategies for ISSNHL using a machine-learning model. Methods: . This retrospective multicenter cohort study was conducted between January 2015 and December 2020, with data analysis performed between January 2021 and March 2024. Patients were selected based on the International Classification of Diseases, 10th Revision criteria for ISSNHL, along with relevant medication and procedure codes. Patients with pure-tone audiogram results not meeting ISSNHL criteria, better initial hearing in the affected ear, an identifiable etiology, no post-treatment audiogram, or delayed treatment (>6 weeks) were excluded. We included 770 patients diagnosed with ISSNHL who received ITSI. The primary outcome was the area under the receiver operating characteristic curve for prediction performance. Recovery status was determined using the last pure-tone audiogram. Modeling was conducted on the Quanta for Medical Care AI platform using five machine-learning algorithms and a nested cross-validation framework, in which feature selection and hyperparameter tuning were performed in the inner folds and model performance was evaluated in the outer folds. Results: . A random forest classifier outperformed the other models in predicting hearing outcomes, achieving an area under the receiver operating characteristic curve of 0.788. Time to ITSI was the most influential treatment-related factor, with ITSI administered within 10 days of hearing loss being associated with better outcomes. This model can be used to provide personalized prognostic estimates under different treatment protocols. Conclusion . The machine-learning-based prediction model facilitates personalized treatment strategies and timely treatment adjustments for ISSNHL, thereby optimizing the likelihood of complete recovery.

Background: Patients with coarctation of the aorta (CoA) and an interrupted aortic arch (IAA) may present with small mitral valves (MVs) and a reduced left ventricular (LV) volume. Biventricular repair (BVR) in these patients is dependent on adequate size of the left cardiac structures.Purpose: This study evaluated the impact of the hemodynamic characteristics of atrial septal defects (ASDs) on MV growth following surgical repair. Methods: We retrospectively reviewed the data of patients diagnosed with CoA or IAA between 2007 and 2024. The z score for MV size measured 6 months postoperatively (Z2) was compared with the preoperative MV size (Z1). The factors associated with MV growth were also studied. Results: A total of 161 patients with CoA or IAA were included. Transthoracic echocardiography was used to assess the MV and LV dimensions preoperatively and 6 months postoperatively. Of the cohort, 155 (96.3%) underwent initial BVR and 6 underwent single-ventricle palliation. MV z scores significantly increased following BVR (mean change: +0.45±1.35; P<0.001) but decreased after single-ventricle repair (-0.56±0.49, P=0.04). Multivariate analysis identified the initial MV z score and ASD pressure gradient as independent predictors of MV growth (R2=0.39). Conclusion Annular growth of the MV was not observed in patients who underwent single-ventricle palliation. In contrast, among patients who achieved BVR, those with a small preoperative MV annulus and low ASD pressure gradient demonstrated subsequent catch-up MV growth, suggesting that adequate left-sided preload is essential for MV development.

Objective To compare the clinical effects of single-puncture and double-puncture subcutaneous tunneling techniques for PICC placement in cancer patients,and to provide references for nurses in selecting appropriate catheterization methods.Methods A continuous sampling method was adopted to select cancer patients who underwent PICC placement in the Department of Oncology at a tertiary general hospital in Nanning from June 2022 to December 2023.According to the actual catheterization technique received by patients,they were assigned to either the single-puncture or double-puncture subcutaneous tunneling group.After 1:1 propensity score matching(PSM),the 2 groups were compared in terms of catheter-related complication rates,pain scores and total catheterization time.Results After propensity score matching,79 patients were included in each group.The results showed that the incidence of catheter-related thrombosis,pain scores,and total catheterization time in the one-needle subcutaneous tunneling group were significantly lower than those in the two-needle subcutaneous tunneling group,with statistically significant differences(P＜0.05).Conclusion The one-needle subcutaneous tunneling method can effectively reduce the incidence of catheter-related thrombosis and pain during catheterization in cancer patients,while also shortening the total catheterization time.

Objective To investigate the value of ultrasound for differentiating pancreatoblastoma(PB)and solid pseudopapillary tumor of pancreas(SPT)in children.Methods Data of 7 children with PB(PB group)and 22 with SPT(SPT group)were retrospectively analyzed.The clinical data and lesion's ultrasonic manifestations were compared between groups.Receiver operating characteristic(ROC)curves of clinical and ultrasound related parameters being significantly different between groups showed by univariate analysis were draw,and the area under the curve(AUC)were calculated to evaluate their efficacy for differentiating PB and SPT.Ultrasound parameters with P＜0.05 in univariate analysis were incorporated into binary logistic analysis,and a ultrasound regression model was constructed to distinguish PB and SPT,and its diagnostic efficacy was evaluated.Results Significant differences of children'age,gender,serum alpha fetoprotein level,and the shape,maximum diameter,texture,calcification and local invasion of lesions were found between groups(all P＜0.05).AUC of single serum alpha fetoprotein level,the shape,maximum diameter,texture,calcification and local invasion of lesion for differentiating PB and SPT was 1.000,0.766,0.854,0.776,0.789 and 0.714,respectively(all P＜0.05).The shape(OR=8.704,P=0.075)and maximum diameter of lesions(OR=1.695,P=0.042)showed with ultrasound were both important differentiating factors for PB and SPT,and AUC of the ultrasound regression model constructed based on them was 0.886.Conclusion Ultrasound could effectively differentiate PB and SPT in children.

AIM To study the chemical constituents from Commelina communis L.METHODS The 95％ethanol extract from C.Communis was isolated and purified by activated charcoal,silica gel,Sephadex LH-20,and HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Seventeen compounds were isolated and identified as p-hydroxyl ethyl cinnamate(1),p-hydroxybenzaldehyde(2),vanillin(3),4-hydroxy-2,3-dimethyl-2-nonen-4-olide(4),hemeratrol A(5),chakyunglupulin B(6),chakyunglupulin A(7),2-(2-hydroxyethyl)-3-methylfumaric acid(8),N-cis-feruloyl tyramine(9),N-trans-coumaroyltyramine(10),5,6,7,3',4',5'-hexamethoxyflavone(11),N-trans-sinapoyltyramine(12),dihydro-feruloyltyramine(13),N-trans-feruloyltyramine(14),2-phenylethanol-β-D-glucoside(15),quercetin-3-O-β-D-glucoside(16),and isorhamnetin-3-O-β-D-glucopyranoside(17).CONCLUSION Compounds 4-8,10 and 11 are isolated from Commelina genus for the first time,and 1,9,12-15 are first isolated from this plant.

AIM To evaluate the quality consistency of Tongmai Granules,Tongmai Tablets,Tongmai Capsules and Tongmai Oral Liquid.METHODS The HPLC fingerprints were established,after which the contents of danshensu,protocatechuic aldehyde,3'-hydroxy puerarin,puerarin,puerarin apioside,daidzin,ferulic acid,salvianolic acid B and salvianolic acid A were determined,and cluster analysis and principal component analysis were adopted in the quality analysis from the perspective of daily intake.RESULTS There were 21 common peaks in the fingerprints for 39 batches of samples with the similarities of 0.765-0.997.Various batches of samples were clustered into 5 categories,2 principal components demonstrated the accumulative variance contribution rate of 83.53％ .The daily intakes of various constituents in different dosage forms exhibited obvious differences,especially for that of salvianolic acid B,which were low in tablets and capsules,and their heterogeneities existed among the same dosage forms.CONCLUSION This simple and accurate method can provide a reference for the quality evaluation of Tongmai preparations from different manufacturers.