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.

ObjectiveTo investigate the contamination status of ochratoxin A (OTA) in commercially available food products in Shanghai, and to assess OTA exposure levels and the associated non-carcinogenic and carcinogenic risks among pregnant women by integrating dietary consumption data of this population. MethodsThe levels of OTA contamination in 1 520 food samples collected in Shanghai from 2022 to 2023 were determined using liquid chromatography-tandem mass spectrometry. An exposure assessment model was developed based on the dietary consumption levels of pregnant women from the 2016‒2017 Shanghai Pregnant Women Dietary Monitoring Survey to calculate the estimated daily intake (EDI) of OTA, the margin of exposure for non-carcinogenic toxicity (MOE₁), and the margin of exposure for carcinogenic toxicity (MOE₂). An MOE₁ greater than 200 and an MOE₂ greater than 10 000 indicate that the non-carcinogenic toxicity and carcinogenic toxicity resulting from exposure are negligible, respectively. For samples with OTA contamination levels below the limit of detection (LOD), which accounted for more than 80% of the samples, the OTA levels were assigned values of 0 and LOD, respectively, for subsequent calculations. ResultsThe detection rates of OTA in cereals, nuts, dried fruits, and alcohol samples collected in 2022 were 2.03%, 0, 0, and 0, respectively. The OTA detection rates in cereals, nuts, dried fruits, beans, and alcohol samples collected in 2023 were 2.50%, 0.39%, 2.47%, 1.67%, and 13.33%, respectively. For pregnant women in Shanghai in 2022, simulation results indicated that when assigning a value of 0 and the LOD, theP₅₀ values of EDI for dietary OTA exposure were 0.05 and 0.72 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.25 and 2.40 ng·(kg·d)^-1, respectively. For pregnant women in Shanghai in 2023, the P₅₀ values of EDI for dietary OTA exposure were 0.04 and 1.00 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.23 and 2.67 ng·(kg·d)^-1, respectively, both substantially below the tolerable daily intake (TDI) for OTA [17 ng·(kg·d)^-1]. The EDI for dietary OTA exposure in 100.0% of Shanghai pregnant women was lower than the TDI, indicating an overall low level of dietary OTA exposure among this population. For 100.0% of pregnant women, the MOE₁ for dietary OTA exposure exceeded 200. When assigned a value of 0, the MOE₂ for 100.0% of pregnant women in both 2022 and 2023 exceeded10 000. When assigned the LOD value, 72.3% and 81.8% of pregnant women in 2022 and 2023, respectively, had an MOE₂ exceeding 10 000. ConclusionFrom 2022 to 2023, samples of cereals, nuts, dried fruits, beans, and alcohol sold in Shanghai exhibited varying degrees of OTA contamination. The overall EDI of OTA exposure among pregnant women in Shanghai remained at a low level. The non-carcinogenic and carcinogenic risks associated with OTA exposure were generally low and at controllable levels.

Objective: To analyze the characteristics and key risk factors of abnormal blood disposal throughout the 2024-2025 blood collection and supply process based on nationwide multi-site monitoring data, develop a comprehensive prevention and control strategy across the entire chain, reduce preventable blood waste, and ensure clinical blood safety. Methods: According to the Guidelines for Haemovigilance (T/CSBT 001-2026), we extracted 74 cases of abnormal blood disposal events reported by the China Blood Transfusion Association′s Blood Safety Monitoring System from January 1 2024, to December 31 2025, and conducted descriptive statistical analysis on the distribution of events, types of deviations, root causes, and classifications of disposal manifestations. Results: A total of 664 adverse events related to blood collection and supply were reported over two years, with 74 cases involving discarded abnormal blood units, accounting for 11.1% of the total. Among these, blood component preparation (40.5%) and blood collection (37.8%) remained traditional high-risk stages. The proportion of blood waste occurring during storage, distribution, and transportation increased from 7.7% in 2024 to 34.3% in 2025. Deviations from standard operating procedures (SOP) by personnel were the primary cause, accounting for 74.3% of cases. Discarded blood units were categorized into four types: compromised closed blood bag systems (40 cases), mainly due to inadequate heat sealing, physical damage, or dropped bags; blood out of the cold chain (12 cases), primarily resulting from blood being left at work sites; imbalanced proportion of preservation solution (10 cases), mostly caused by blood collection volumes exceeding the standard capacity of blood bags; and other causes (12 cases). Conclusion: Human operational errors are the core cause of abnormal blood waste. The collection and preparation stages have long been at high-risk, and the risks in the storage and transportation stages have been increasing year by year. We should focus on standardizing personnel management, improving specialized operation norms such as heat sealing, transportation, and storage, establishing a full-process intelligent cold chain monitoring and multi-node visual verification mechanism, and systematically reducing the occurrence rate of abnormal blood waste through a closed-loop quality intervention system, thereby improving the utilization efficiency of voluntary blood donation resources.

ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

Objective To study the pharmacokinetic profile of zidovudine and lamivudine tablets(ZL)in Chinese healthy subjects and to evaluate its bioequivalence and safety.Methods A randomized,open,single-dose,two-sequence,four-cycle and fully replicated crossover bioequivalence trial was conducted in 32 healthy subjects both fasting and postprandial,and two preparations of ZL tablets were administered orally in each cycle,with a washout period of 5 days.The concentrations of zidovudine and lamivudine in plasma were determined using high performance liquid chromatography-tandem mass spectrometry.The pharmacokinetic evaluation index parameters were statistically analyzed using Phoenix WinNonlin version 8.1 data statistical software to evaluate bioequivalence.Results The Cmax of zidovudine under fasting and postprandial conditions between ZL and the reference drugs after a single dose were(3 782.499±1 921.649)vs.(3 543.164±1 946.076)ng·mL-1 and(1 585.827±914.246)vs.(1 667.595±862.945)ng·mL-1,respectively.And the AUC0-t for fasting and postprandial conditions of zidovudine was(3 177.091±819.538)vs.(3 071.375±972.145)h·ng·mL-1 and(2 437.999±478.147)vs.(2 402.725±477.792)h·ng·mL-1,respectively;while the AUC0-∞ were(3 225.674±825.131)vs.(3 093.448±972.340)h·ng·mL-1and(2 464.310±480.790)vs.(2 427.693±477.933)h·ng·mL-1,respectively.The Cmax of a single dose of lamivudine under fasting and postprandial conditions between ZL and the reference drugs were(1 923.329±490.572)vs.(1 830.570±476.947)ng·mL-1 and(1 922.711±589.130)vs.(1 881.857±527.577)ng·mL-1,respectively.The AUC0-t for preprandial and postprandial lamivudine was(7 598.265±1 376.774)vs.(7 283.422±1 356.146)h·ng·mL-1 and(7 554.169±958.379)vs.(7 329.376±924.075)h·ng·mL-1,respectively,whereas the AUC0-∞ were(7 734.038±1 326.907)vs.(7 405.088±1 340.036)h·ng·mL-1 and(7 660.916±958.694)vs.(7 435.102±930.448)h·ng·mL-1,in fasting and fed tests,the 90％confidence intervals(CI)of the geometric mean ratios of the main pharmacokinetic parameters between test and reference preparations were all within the range of 80％-125％,respectively.A total of 37 adverse events occurred during the trial period,including 21 in the fasting group and 16 in the postprandial group,and no serious adverse events occurred.Conclusion The test formulations of zidovudine and lamivudine tablets were bioequivalent and well tolerated in healthy Chinese subjects under fasting and fed conditions compared to the reference tablets.

Objective To systematically evaluate the effect of inspiratory muscle training(IMT)on weaning outcomes in patients with weaning failure.Methods Literatures in Chinese and English were retrieved from databases such as PubMed,Cochrane Library,Web of Science,Embase,CNKI,VIP,Wanfang data and CBM for researches on the effect of IMT in mechanical ventila-tion weaning failure,from the inception of the databases to October 22,2024.The methodological quality of the researches was evaluated with PEDro scale,and data were extracted for a systematic review.Results Nine randomized controlled trials were included,published between 2011 and 2023,from Brazil,China,the United States,Iran and Australia,with a total of 499 patients.The scores of the PEDro scale ranged five to eight.The population included patients with prolonged weaning,difficult weaning and tracheostomy.The IMT methods included threshold load training and tapered flow resistance training.The training intensity was 30%to 80%of maximal inspiratory pressure(MIP),and some researches did not set the training intensity based on MIP.The pro-gression of intensity varied widely across researches.The intervention frequency ranged from five to 30 breaths per set,with at least one minute rest between sets,two to six sets per session,one to two sessions per day,and five to seven days per week.The duration of the intervention ranged from successful weaning,one week after weaning,extubation,or four days to eight weeks.Regarding the efficacy of the intervention,IMT was not benefi-cial for the duration of mechanical ventilation and intensive care unit(ICU)length of stay on weaning failure pa-tients.However,the effect of IMT on weaning successful rates,duration of weaning,MIP and mortality was in-consistent.Conclusion IMT can not improve the duration of mechanical ventilation and ICU length of stay for weaning failure pa-tients,and there is still debate regarding its effect on successful rate of weaning,duration of weaning,MIP and mortality.

Objective:To investigate the short-term clinical efficacy of implantation with a 3D-printed microporous titanium prosthesis in the treatment of large segmental infectious tibial defects.Methods:A retrospective analysis was conducted of the electronic medical records of the 47 patients with large segmental tibial defects who had been treated with 3D-printed microporous titanium prostheses at Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force from January 2019 to February 2024. The cohort included 36 males and 11 females, with an age of (46.2±11.8) years and a mean bone defect length of 12.3 (8.0, 16.8) cm. In the 19 patients complicated with soft tissue defects, the area of soft tissue defects ranged from 10.0 cm × 6.0 cm to 33.0 cm × 10.0 cm. For the 28 patients without soft tissue defects at the lower leg, the bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage; for the 19 patients complicated with soft tissue defects, the soft tissue defects at the lower limb were repaired using an anterolateral thigh flap with vascular anastomosis at the same time when bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage. After infection control at 2 to 8 months after surgery, individualized 3D-printed microporous titanium prostheses were implanted at the second stage to reconstruct the bone defects. Postoperative observations included the patients' first standing time, crutch walking time, full weight-bearing time, osseointegration of the tibial fracture and the prosthesis, and complications during follow-up.Results:The follow-up period for the 47 patients was (34.7±14.3) months. The first standing time was (2.2±0.6) months, crutch walking time (3.8±1.1) months, and full weight-bearing time (5.3±1.2) for this cohort. The evaluation by the Paley's bone healing score resulted in 25 excellent cases, 18 good cases, 1 medium case, and 3 poor cases, giving an excellent and good rate of 91.5% (43/47). One year after operation, the X-ray films showed that the tibial fractures and prostheses were well integrated in the 43 patients. Two patients developed recurrent tibial infection which was responded to replacement of the vancomycin-loaded calcium sulfate spacer. The fixation screws for tibial prosthesis were broken in one patient, but no recurrence of infection was observed after revision. The overall incidence of complications was 6.4% (3/47).Conclusion:In the treatment of large segmental infectious tibial defects, by facilitating rapid functional recovery and ensuring a low incidence of complications, implantation with a 3D-printed microporous titanium prosthesis demonstrates fine short-term clinical efficacy.

An implantable cardiac monitor(ICM)is a subcutaneous electronic device for recording and remotely transmitting electrocardiographic events.New-generation ICM,like the Reveal LINQ,have extended arrhythmia monitoring duration and improved diagnostic yield through miniaturization,large storage capacity,and easy implantation.They provide comprehensive monitoring data for cardiovascular disease diagnosis and treatment,optimize individualized treatment plans,and enhance patient prognosis.In recent years,research on ICM in cardiovascular fields has deepened,and their clinical application scope has expanded.They show significant advantages and unique value and are widely used in early cardiovascular disease diagnosis and prognostic management.In the future,ICM are expected to play a bigger role in boosting diagnostic and prognostic capabilities for cardiovascular disease patients,offering stronger support for early disease detection,accurate diagnosis,and effective management.

Objective To systematically evaluate the effect of inspiratory muscle training(IMT)on weaning outcomes in patients with weaning failure.Methods Literatures in Chinese and English were retrieved from databases such as PubMed,Cochrane Library,Web of Science,Embase,CNKI,VIP,Wanfang data and CBM for researches on the effect of IMT in mechanical ventila-tion weaning failure,from the inception of the databases to October 22,2024.The methodological quality of the researches was evaluated with PEDro scale,and data were extracted for a systematic review.Results Nine randomized controlled trials were included,published between 2011 and 2023,from Brazil,China,the United States,Iran and Australia,with a total of 499 patients.The scores of the PEDro scale ranged five to eight.The population included patients with prolonged weaning,difficult weaning and tracheostomy.The IMT methods included threshold load training and tapered flow resistance training.The training intensity was 30%to 80%of maximal inspiratory pressure(MIP),and some researches did not set the training intensity based on MIP.The pro-gression of intensity varied widely across researches.The intervention frequency ranged from five to 30 breaths per set,with at least one minute rest between sets,two to six sets per session,one to two sessions per day,and five to seven days per week.The duration of the intervention ranged from successful weaning,one week after weaning,extubation,or four days to eight weeks.Regarding the efficacy of the intervention,IMT was not benefi-cial for the duration of mechanical ventilation and intensive care unit(ICU)length of stay on weaning failure pa-tients.However,the effect of IMT on weaning successful rates,duration of weaning,MIP and mortality was in-consistent.Conclusion IMT can not improve the duration of mechanical ventilation and ICU length of stay for weaning failure pa-tients,and there is still debate regarding its effect on successful rate of weaning,duration of weaning,MIP and mortality.