ObjectiveTo generate cynomolgus and rhesus monkey models carrying the Booroola fecundity (FecB) variant of bone morphogenetic protein receptor type 1B (BMPR1B) gene (designated BMPR1B^FecB) using adenine base edit technology and to explore genetic improvement strategies for enhancing the reproductive performance of laboratory macaques. MethodsFour single-guide RNAs (sgRNAs) were designed to target the BMPR1B c.746A>G locus in cynomolgus and rhesus monkeys. The sgRNAs were combined with the ABE8e-SpRY base editor, and the resulting editing complexes were microinjected into zygotes of both macaque species. Following in vitro culture of the injected embryos, nested PCR amplification was performed to detect the base-editing efficiency at the target site to screen for highly efficient sgRNAs. Subsequently, normally developing gene-edited embryos were transferred into the oviducts of surrogates. Seven days after birth, ear skin or peripheral blood samples were collected from the newborn monkeys for genotyping and mosaicism analysis, and the growth, development, and health status of the gene-edited monkeys were monitored. ResultsAmong the four candidate sgRNAs, sgRNA4 was identified as achieving 100% editing efficiency at the c.746A>G site. A total of 17 live monkey offspring were obtained via embryo transfer, including 8 cynomolgus monkeys and 9 rhesus monkeys. Genotyping results showed that all 8 newborn cynomolgus monkeys carried the c.746A>G point mutation, with an editing efficiency of 100% (8/8), of which 37.50% (3/8) were mosaics. Among the 9 newborn rhesus monkeys, 8 individuals carried the c.746A>G mutation, with an editing efficiency of 88.89% (8/9), of which 75.00% (6/8) were mosaics. ConclusionThe ABE8e-SpRY base-editing system enables precise editing at the c.746A>G (p.Q249R) locus of the BMPR1B gene in both cynomolgus and rhesus monkey embryos, resulting in the successful establishment of laboratory monkey models carrying the BMPR1B^FecB variant. These models provide a valuable foundation for future studies of the regulatory role of the BMPR1B^FecB variant in reproductive performance at the non‑human primate level, as well as for exploring genetic improvement strategies to enhance reproductive performance in laboratory monkeys.

Background With the unprecedented development of aviation business, the work load and job burnout of airport employees are becoming more and more serious, and the impact on sleep quality needs to be addressed. Objective To explore the current situation of work load and sleep quality of airport employees, and whether job burnout plays a role in the relationship between the two variables. Methods During September 2023, a cross-sectional survey was conducted among employees of an airport in Hunan Province, and 1503 employees were surveyed. A basic information questionnaire, a work load measurement questionnaire, Maslach Burnout Inventory General Survey, and Pittsburgh Sleep Quality Index were used in the survey. Logistic regression was used to analyze the influencing factors of sleep quality. SPSS 25.0 PROCESS v4.1 plug-in was used to analyze the mediating effect of job burnout. Results A total of 1503 questionnaires were distributed in this study, and 1424 valid questionnaires were recovered, with a recovery rate of 94.7%. The rate of heavy work load was 50.0% (712/1424), the rate of job burnout was 74.6% (1062/1424), and the rate of sleep disorders was 58.7% (836/1424). The results of logistic regression analysis showed that individuals with job burnout had a 1.734 times higher risk of reporting sleep disorders compared to those without job burnout (95% CI: 1.306, 2.302); compared to those with light work load, individuals with heavy work load have a higher risk of sleep disorders (OR=3.422, 95%CI: 2.639, 4.437). The results of mediating effect test indicated a work load-burnout-sleep quality pathway (P <0.001), with a mediation effect value of 0.1052 (95%CI: 0.019, 0.067), accounting for 18.02% of the total effect. Conclusion The rate of job burnout and the rate of reporting poor sleep quality are high among airport employees, and job burnout plays a mediating role in the relationship between work load and sleep quality. Adopting measures to reduce work load and reduce burnout can improve the sleep quality of airport employees.

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Objective To observe the feasibility of photon-counting detector(PCD)-CT combined with"four-lows"protocol(low contrast agent concentration,low contrast dose,low contrast agent flow rate,low radiation dose)for coronary CT angiography(CCTA).Methods Totally 106 patients with suspected coronary artery disease were prospectively enrolled and randomized into energy-integrating detector(EID)-CCTA(group A,using conventional scanning protocol,n=52)or PCD-CCTA(group B,using"four-lows"scanning protocol,n=54)groups and underwent relative examinations.The radiation dose,subjective and objective evaluation results of imaging quality were compared between groups.Results The contrast agent dose and flow rate,volume CT dose index,dose length product and effective dose in group B were all lower than those in group A(all P＜0.001).The subjective scores in group B were higher than in group A(5[4,5]vs.4[4,5],Z=-2.310,P=0.021).Compared with group A,CT value,signal-to-noise ratio and contrast-to-noise ratio of aortic root and most of the main branches of coronary arteries increased in group B,while standard deviation of CT value decreased(all P＜0.05).Conclusion PCD-CT combined with"four-lows"protocol could be used for CCTA,which could improve imaging quality and reduce contrast agent usage and radiation dose.

Objective:To assess the viability of reducing radiation dose, contrast media volume, injection flow rate and contrast medium concentration (quadruple low-dose protocol) by utilizing virtual monoenergetic images (VMI) in photon-counting detector CT (PCD-CT) for aortic CT angiography (CTA), while maintaining image quality in comparison to images obtained from energy-integrating detector CT (EID-CT).Methods:From April 2024 to June 2024, a total of 40 participants who underwent aortic CTA on PCD-CT were prospectively enrolled in the experimental group (PCD-CT group), while 40 patients with similar baseline characteristics who had previously undergone aortic CTA using EID-CT were retrospectively selected for the conventional group (EID-CT group). The EID-CT group used a tube voltage of 90 kVp, a contrast media volume of 60 ml of contrast, an injection flow rate of 3 ml/s, and a contrast concentration of 350 mgI/ml; the PCD-CT group used the QuantumPlus mode, with a tube voltage of 140 kVp, a total amount of iodine in the contrast media of 140 mgI/kg, and an injection flow rate=contrast media volume/(delay time+scan time), and a contrast media concentration of 320 mgI/ml. VMIs in PCD-CT group were reconstructed in 5-keV intervals ranging from 45 to 65 keV. The effective radiation dose and contrast injection protocols were recorded and compared between two groups. Objective image quality assessment was performed for each group. CT attenuation, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured at five anatomical locations (ascending aorta, aortic arch, descending aorta, abdominal aorta, and right common iliac artery), and image noise was recorded. Subjective image quality was independently evaluated by two readers using a 5-point Likert scale in a blinded manner. Based on data normality, the one-way ANOVA or Kruskal-Wallis test was used for image quality assessment, with Bonferroni-corrected post-hoc analysis for multiple comparisons.Results:There were no significant differences in the baseline characteristics between two groups (all P0.05). The PCD-CT group demonstrated significantly lower effective radiation dose [(3.88±0.65) mSv vs. (5.97±1.15)mSv], contrast media volume [(29.25±4.56) ml vs. 60 ml], and injection rate [(2.65±0.42) ml/s vs. 3 ml/s] than the EID-CT group, with reductions of 35%, 51%, and 12%, respectively (all P0.001). For objective image quality, except for the ascending aortic CT attenuation, the CT attenuation, SNR, and CNR of other vessels in the 55 keV PCD-CT group were comparable to those in the EID-CT group. Additionally, the difference in image noise between these two groups was not statistically significant ( P0.05). Concerning subjective image quality, at 55 keV, the PCD-CT group had similar image noise scores and vessel attenuation scores (both P0.05) and better visualization of renal artery branching ( P=0.001) compared to the EID-CT group. Conclusion:In comparison to EID-CT, the use of a 55 keV image in PCD-CT for aortic CTA has demonstrated reductions in radiation dose, contrast media volume, injection flow rate and contrast medium concentration, while maintaining image quality.

Objective:To evaluate the feasibility of head and neck vascular imaging using photon-counting detector computed tomography (PCD-CT) combined with a “quadruple lows” protocol—characterized by low contrast media volume, low iodine concentration, low injection rate, and low radiation dose—and to compare the image quality with that obtained by energy-integrating detector CT (EID-CT).Methods:A total of 105 patients with suspected cerebrovascular disease were prospectively enrolled at the First Affiliated Hospital of Zhengzhou University between April and June 2024. Patients were randomly assigned to three groups ( n=35). Group A underwent conventional head and neck CTA using EID-CT. Group B underwent PCD-CT with a protocol involving ultra-low contrast media volume, low iodine concentration, and low injection rate. Group C underwent PCD-CT with the full “quadruple low” protocol. Objective image quality parameters—including CT attenuation, image noise (standard deviation, SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR)—were measured at the ascending aorta, common carotid artery, internal carotid artery, vertebral artery, basilar artery, posterior cerebral artery, and middle cerebral artery. Two radiologists independently rated subjective image quality using a 5-point Likert scale. Differences among groups were analyzed using one-way ANOVA and the Kruskal-Wallis test. Results:Compared to Group A [contrast volume: (42.78±6.64)ml], contrast agent volume was significantly reduced in Groups B and C[ (26.26±4.45) ml and (26.54±3.83)ml, respectively], demonstrating reductions of 39% and 38% (both P<0.01). The iodine concentration was 320 mg/ml in Groups B and C, lower than 350 mg/ml in Group A (8.5%). The injection rate was also reduced in Groups B and C [(3.39±0.61) and (3.55±0.51)ml/s, respectively] compared to Group A [(4.28±0.66) ml/s], with reductions of 21% and 17% (both P<0.01). The effective dose (ED) was similar between Groups A and B [(1.40±0.15) vs. (1.40±0.19)mSv, P>0.05], while Group C demonstrated a significantly lower ED [(0.99±0.09) mSv], with a reduction of 30% compared to Group A and 29% compared to Group B (both P<0.01).In terms of objective image quality, significant differences in image noise (SD) were observed among the three groups at the vertebral artery, internal carotid artery, posterior cerebral artery, and middle cerebral artery (all P<0.05). Groups B and C showed significantly lower SD compared to Group A ( P<0.05), with no significant difference between B and C ( P>0.05). SNR was significantly higher in Groups B and C than in Group A at multiple vascular segments (all P<0.05). CNR differed only at the internal carotid artery, where Groups B and C demonstrated superior performance compared to Group A ( P<0.05).Subjective image quality scores showed no significant difference between Groups A and C ( P>0.05), while Group B had significantly higher scores than both A and C ( P<0.05). All images were deemed diagnostically acceptable. Conclusion:Compared with conventional EID-CT, PCD-CT combined with a “quadruple lows” protocol enables substantial reductions in contrast media and radiation dose while further improving image quality in head and neck CTA.

Objective To investigate the therapeutic efficacy of HLA-genotype matched platelet transfusion using a platelet donor database for severe platelet transfusion refractoriness (PTR) caused by HLA antigen-antibody incompatibility. Methods Using real-time quantitative PCR (qPCR) to identify he patient's HLA class I genotype, followed by searching the platelet donor database for matching donors, and selecting highly compatible donors for transfusion. Platelets with higher compatibility levels were prioritized for transfusion recommendations. Results Among the 19 patients studied, 7 patients identified donors with B2U or higher compatibility, 6 patients identified donors with BX or higher compatibility, and 6 patients did not find a suitable donor. The transfusion efficacy was evaluated by calculating the corrected count increment (CCI) 24 hours post-transfusion, and all transfusions were effective. Conclusion The optimal strategy to prevent and treat patients with severe platelet transfusion refractoriness is to ensure patients receive platelet transfusions that are matched to their HLA genes, and this approach significantly enhances transfusion efficacy.
Humans ; Platelet Transfusion/adverse effects* ; HLA Antigens/immunology* ; Male ; Middle Aged ; Female ; Adult ; Blood Platelets/immunology* ; Aged ; Genotype

Objective To identify the sequence variation of human leukocyte antigen(HLA)novel allele A11:193 and to simulate the three-dimensional structure of the protein molecule.Methods A sample with abnormal allele results was found by PCR-SBT sequencing and identified by single allele specific sequencing.The 3D structure of the encoded protein was analyzed by Swiss-Model.Results Compared with HLA-A*11:01:01,which has the highest homology,exon 4 nt 662 of this sample has a base substitution of A→G,and its corresponding codon 197 is changed from CAT to CGT,which is changed from histidine(His)to arginine(Arg).Conclusion A new allele of HLA-A was confirmed.The allele sequence was named HLA-A11:193 by the WHO HLA Factor Nomenclature Committee and the three-dimensional structure of the protein molecule encoded by HLA-A11:193 was simulated.There was no significant difference in the three-dimensional structure of the encoded protein between it and HLA-A*11:01:01.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Objective To identify the sequence variation of human leukocyte antigen(HLA)novel allele A11:193 and to simulate the three-dimensional structure of the protein molecule.Methods A sample with abnormal allele results was found by PCR-SBT sequencing and identified by single allele specific sequencing.The 3D structure of the encoded protein was analyzed by Swiss-Model.Results Compared with HLA-A*11:01:01,which has the highest homology,exon 4 nt 662 of this sample has a base substitution of A→G,and its corresponding codon 197 is changed from CAT to CGT,which is changed from histidine(His)to arginine(Arg).Conclusion A new allele of HLA-A was confirmed.The allele sequence was named HLA-A11:193 by the WHO HLA Factor Nomenclature Committee and the three-dimensional structure of the protein molecule encoded by HLA-A11:193 was simulated.There was no significant difference in the three-dimensional structure of the encoded protein between it and HLA-A*11:01:01.