Objective: To report the antibody identification, blood management during pregnancy and the monitoring process of fetal hemolytic disease of fetus and newborn (HDFN) in a pregnant woman with a history of blood transfusion and pregnancy who developed anti-Jr . Methods: Saline tube technique and anti-human globulin technique were used for maternal blood typing, unexpected antibody screening and identification, as well as for determining antibody titer and IgG subclasses. PCR-SSP was employed for genotyping of 18 blood group systems. Next-generation sequencing (NGS) was utilized for gene sequencing of 38 blood group systems. Sanger sequencing was applied to verify rare blood group mutations detected by NGS and to investigate the corresponding rare blood group genes in family members. Blood preparation was achieved through anemia management in prenatal clinics and autologous blood collection during pregnancy. The newborn underwent the three primary tests for HDFN and plasma IgG subclass testing. Results: The pregnant woman's blood type was B, RhD positive, with a positive unexpected antibody screen, and the antibody identification pattern was consistent with a high-frequency antigen antibody. Gene sequencing revealed a homozygous ABCG2 c.376C>T mutation in the woman, resulting in the Jr(a-) phenotype, and anti-Jr antibody was present in her plasma. No compatible Jr(a-) blood was found among family members. The maternal anti-Jr IgG titer remained stable at 256 during pregnancy, with no detectable IgG1 or IgG3 subclasses against the Jr antigen. A total of 800 mL of autologous blood was collected in two stages during pregnancy. The newborn was B, RhD positive, Jr(a+), with a positive unexpected antibody screen (anti-Jr ). IgG subclass typing detected no IgG1 or IgG3. The direct antiglobulin test was positive, while the acid elution test was negative. Conclusion: The combination of serology and blood group genetic analysis provides a diagnostic basis for identifying antibodies to high-frequency antigens. Managing perinatal anemia and implementing staged autologous blood storage can secure blood supply for the perioperative period. IgG antibody subclass typing offers a reference for clinical assessment and prevention of HDFN.

Triclosan (TCS) and triclocarban (TCC) are widely used synthetic broad-spectrum antibacterial agents that can enter the human body through the skin, gastrointestinal tract, and other pathways. More and more studies have found that exposure to TCS and TCC can affect human health, but currently, review reports on the health effects of human exposure to TCS and TCC are limited. Therefore, this study reviewed population studies on the relationship between TCS and TCC exposure and health effects by searching the PubMed database, summarized the associated health outcomes, and elucidated the biological mechanisms. A total of 56 studies were retrieved, among which cross-sectional studies (25 studies, 44.64%) and cohort studies (25 studies, 44.64%) accounted for a relatively large proportion, while case-control studies (6 studies, 10.72%) were relatively few. Studies on TCS exposure (48 studies, 85.71%) were far more prevalent than those on TCC exposure (2 studies, 3.57%). The remaining 6 studies involved both TCS and TCC exposure. The research results revealed that TCS exposure was associated with male and female abnormal reproductive functions, fetal growth restriction, abnormal behavior development in children, obesity, gestational diabetes mellitus (GDM), and immune-related diseases. Although the results of different studies show significant differences, they have indicated that exposure to TCS is a potential risk factor for these health problems. Due to the limited number of studies, the evidence for the relationship between TCC exposure and most of the aforementioned health effects is insufficient. Population studies and in vitro and in vivo studies have shown that exposure to TCS and TCC can interfere with the microbial homeostasis, the endocrine system, oxidative stress and immune function of the body, which are potential mechanisms causing adverse health effects. In the future, large-scale prospective cohort studies, as well as in vivo and in vitro studies, are still needed to further clarify the associations between TCS and TCC exposure and health effects, and to deeply explore its mechanism of action. These efforts will provide references for clarifying the human health hazards of TCS and TCC exposure and formulating targeted prevention and control strategies.

Objective To explore the prognostic value of hyperdense artery sign(HAS)in elderly patients with acute anterior LVO in anterior circulation undergoing mechanical thrombectomy.Methods A single-center retrospective analysis was conducted on 109 patients with acute LVO of anterior circulation admitted in our department from January 2019 to December 2022.According to their preoperative plain CT scans,they were divided into HAS positive(39 patients)and HAS negative(70 patients)groups.Baseline features,surgical indicators,complications and outcomes were compared between the two groups.Results The patients with HAS had significantly larger proportions of atrial fibrillation and symptomatic intracranial hemorrhage than those without the sign(53.8％vs 31.4％,20.5％vs 5.7％,P＜0.05).The rate of 90-day good prognosis was a little higher in the HAS positive group than the negative group,though no statistical difference(48.7％vs 38.6％,P＞0.05).Male,stroke history,SBP,NIHSS at admission,HAS positivity,revasculiza-tion,and symptomatic intracranial hemorrhage were independent influencing factors for favorable prognosis in the patients(P＜0.05,P＜0.01).Conclusion The presence of HAS is a prognostic marker for patients with acute LVO in anterior circulation undergoing mechanical thrombectomy,and it is associated with a higher risk of symptomatic intracranial hemorrhage.

Objective:To investigate the magnetic resonance imaging (MRI) features of non-midline atypical medulloblastoma (MB) in children and analyze the causes of misdiagnosis, so as to improve the understanding and diagnosis of MB.Methods:The clinical and imaging data of 12 cases with non-midline atypical MB confirmed by pathology in Hunan Children′s Hospital from September 2018 to August 2023 were retrospectively analyzed. 12 cases underwent MRI plain scan, 11 cases underwent enhanced scan, and 10 cases underwent diffusion weighted imaging (DWI) and magnetic sensitivity weighted imaging (SWI). The location, morphology, peritumoral edema, size, signal characteristics (cystic lesion or hemorrhage), diffusion and enhancement of the tumor were observed, and the causes of misdiagnosis were analyzed.Results:Among the 12 cases, 9 cases were single, 4 cases were located in the cerebellar hemisphere, 2 cases were in the cerebellopontine angle (CPA), 2 cases were in the brain stem and CPA, and 1 case was in the left parietal lobe. There were 3 cases of multiple lesions, 1 case was located in the right pontine arm and cerebellar hemisphere (2 masses), 1 case was multiple lesions in bilateral cerebellar hemisphere, and 1 case was multiple nodular lesions in the cerebellar vermis mass and left cerebellar hemisphere. 6 cases were irregular in shape and 6 cases were quasi-circular. There were 3 cases without cystic change and 9 cases with varying degrees of cystic change (5 with large cystic change and 4 with small cystic change). 3 cases of hemorrhage, no calcification, 10 cases of DWI showed varying degrees of limited diffusion; 11 cases of enhanced scanning showed mild to obvious enhancement; There were 2 cases without peritumoral edema and 10 cases with mild to moderate peritumoral edema. There were 11 cases with supratentorial hydrocephalus and interstitial cerebral edema, and 1 case without hydrocephalus. 5 cases complicated with subtonsillar hernia; 9 cases were misdiagnosed before operation. Among them, 3 cases were misdiagnosed as high-grade glioma, 3 as low-grade glioma (1 of which was diagnosed as hair-cell astrocytoma), 2 as ependymoma, and 1 as atypical teratoma/rhabdomyoma.Conclusions:The MRI manifestations of non-midline atypical MB in children are varied. Combined with the location of the disease, age and focal signal characteristics, non-midline atypical MB can be included in the diagnostic range after the exclusion diagnosis, which can improve the preoperative diagnosis accuracy of this disease.

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 analyze the efficacy and safety of ustekinumab(UST)in patients with moderate-to-severe Crohn's disease(CD),and to identify factors influencing clinical outcomes.Methods Data were retrospectively collected from patients with moderate-to-severe CD treated with UST in the First Affiliated Hospital of Zhejiang Chinese Medical University and Hangzhou Hospital of Traditional Chinese Medicine between November 2020 and May 2023.Patients were categorized into first-line(not treated with biologic agents,n=68)and second-line(treated with biologic agents,n=66)treatment groups based on prior use of biologic agents.Baseline characteristics,including age,sex,smoking status,disease duration,age at diagnosis,lesion site,disease behavior,perianal disease,history of intestinal surgery,and CD-related drug use,were compared between the two groups.Crohn's disease activity indices(CDAI)were recorded at baseline,week 14,and week 52 to assess the clinical efficacy at weeks 14 and 52.Endoscopic evaluations were performed at baseline and week 52 to evaluate endoscopic efficacy at week 52.The 52-week drug persistence rate and safety profile were also analyzed.Influencing factors related to clinical outcomes were evaluated using univariate and multivariate logistic regression.Results A total of 134 patients with moderate-to-severe CD treated with UST were included.At week 14,clinical response and remission rates were 75.4%(101/134)and 33.6%(45/134),respectively,with no significant difference in clinical efficacy between first-line and second-line groups(clinical response rate:77.9%vs.72.7%,P=0.484;clinical remission rate:38.2%vs.28.8%,P=0.247).At week 52,clinical response and remission rates were 79.9%(107/134)and 56.0%(75/134),respectively.The rates of endoscopic response and remission were 70.9%(95/134)and 38.8%(52/134),respectively.There were no significant differences in clinical efficacy(clinical response rate:80.9%vs.78.8%,P=0.763;clinical remission rate:60.3%vs.51.5%,P=0.306)and endoscopic efficacy(endoscopic response rate:76.5%vs.65.2%,P=0.149;endoscopic remission rate:42.6%vs.34.8%,P=0.354)between the two groups.The 52-week drug persistence rate was 85.8%(115/134),and the adverse reaction rate was 4.5%(6/134).Compared with first-line treatment group,biologic-experienced patients had a significantly higher proportion of dose-optimized therapy in second-line treatment group(45.5%vs.22.1%,P=0.004).Multivariate logistic regression showed that the 14-week clinical response was a significant predictor of 52-week clinical remission,while perianal disease and intestinal surgery history were significant factors associated with treatment failure(P<0.05).Conclusions UST demonstrates significant efficacy in improving clinical and endoscopic outcomes for moderate-to-severe CD patients,with a favorable safety profile.Clinical response at 14 weeks is strongly predictive of clinical remission at 52 weeks.Patients with perianal disease or a history of intestinal surgery were at higher risk of treatment failure.

Objective To investigate the factors influencing global longitudinal strain(GLS)measured by cardiac magnetic resonance(CMR)in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods Clinical data of 315 hospitalized patients diagnosed with acute STEMI who underwent percutaneous coronary intervention(PCI)at the First Medical Center of Chinese PLA General Hospital from June 2016 to September 2021 were retrospectively collected.After analyzing CMR images of all patients,GLS and other strain parameters were obtained,and then the patients were divided into two groups according to the median GLS.In order to balance gender and age differences,1:1 propensity score matching was performed,and 206 patients were eventually included:GLS>-11.3%group(indicating severe GLS impairment,n=103)and GLS≤-11.3%group(n=103).Baseline characteristics,laboratory indicators,coronary angiographic parameters,electrocardiogram(ECG)features,and CMR parameters were compared between the two groups.Variables showing significant differences were analyzed for their correlation with GLS.Multivariate logistic regression and multiple stepwise linear regression analyses were performed to identify factors associated with GLS impairment.Results Compared with GLS≤-11.3%group,GLS>-11.3%group had significantly higher peak levels of creatine kinase-MB(CK-MB)and troponin T(TnT)(P<0.001).A higher proportion of patients in GLS>-11.3%group had the left anterior descending artery(LAD)as the culprit vessel,while a lower proportion had the right coronary artery(RCA)as the culprit vessel(P<0.001).Additionally,GLS>-11.3%group had longer QRS duration(P<0.001)and a higher incidence of pathological Q waves(P=0.001).Regarding CMR parameters,GLS>-11.3%group exhibited larger global circumferential strain(GCS),infarct size(IS),and left ventricular end-systolic volume(LVESV),as well as lower global radial strain(GRS)and left ventricular ejection fraction(LVEF)(P<0.001).Multivariate logistic regression indicated that peak TnT(OR=1.092,P=0.001),LAD culprit vessel(OR=3.744,P<0.001),and QRS duration(OR=1.026,P<0.001)were significantly associated with severely impaired GLS.Multiple stepwise linear regression analysis showed that the logarithmic value of peak TnT,LAD as the culprit vessel,and the square root of QRS duration were linearly correlated with GLS values(adjusted R2=0.301,P<0.001),and these independent variables explained 30.1%of the variation in GLS.Conclusion Elevated peak TnT,prolonged QRS duration,and LAD as the culprit vessel are significantly associated with severe GLS impairment in STEMI patients,indicating more severe myocardial infarction and worse left ventricular function.

In 2024,the U.S.Defense Advanced Research Projects Agency(DARPA)intensified its deployment and management of biotechnological defense applications that involved four major domains:combat effectiveness enhancement,biosecurity defense,development of military materials,and intelligent biotechnology.This paper conducts an in-depth analysis of DARPA's 2024 biotech advancements to provide a reference for related research and development in China.

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 understand the occurrence of different patterns of multimorbidity among children and adolescents aged 9-18 in Tianjin City and analyze the cumulative effects of lifestyle on these patterns of multimorbidity.Methods:From September to November 2022, a stratified cluster random sampling method was used to select students from primary schools, junior high schools, general high schools, and vocational schools in 16 districts of Tianjin to screen for height, weight, blood pressure, distant vision, and diopter. One year later, a follow-up measurement and questionnaire survey were conducted. The log-binomial model was used to analyze the strength of the association between lifestyle factors and different patterns of multimorbidity.Results:The age of 9 488 students was (12.37±2.49) years old, including 4 999 boys and 4 489 girls. The detection rates of three patterns of multimorbidity of overweight obesity and high blood pressure, overweight obesity and myopia, and overweight obesity with high blood pressure and myopia were 6.63%, 9.32%, and 4.21%, respectively. The detection rates of the three types of multimorbidity in boys were higher than those in girls (all P<0.001). The detection rate of overweight obesity and high blood pressure in suburban areas was higher than that in urban areas ( P=0.002). The detection rate of overweight obesity and myopia in suburban areas was lower than that in urban areas ( P=0.034). The detection rate of overweight obesity and myopia among those aged 9-12 years old was higher than other age groups (all P<0.001). The ARR (95% CI) for the association between favorable physical activity and the occurrence of overweight obesity and high blood pressure was 0.79 (0.68-0.92). The ARR (95% CI) for the association between favorable physical activity and the occurrence of overweight obesity with high blood pressure and myopia was 0.82 (0.67-0.99). Compared with children and adolescents with 0-2 favorable lifestyle factors, those with 4-5 favorable lifestyle factors had a lower risk of overweight obesity and high blood pressure ( ARR=0.84, 95% CI: 0.59-0.92). Conclusion:Boys aged 9-18 in Tianjin City are more prone to multimorbidity of overweight obesity and high blood pressure, overweight obesity and myopia, and overweight obesity with high blood pressure and myopia. Children and adolescents with 4-5 favorable lifestyle factors have a reduced risk of occurrence of overweight obesity and high blood pressure. Lifestyle has cumulative effects on multimorbidity of overweight obesity and high blood pressure.