Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Objective To explore the association of the TSLP gene polymorphisms at rs3806932,rs11466741 and rs2289278 loci with childhood asthma and serum TSLP levels,and to analyze the effects of gene-environment interactions on asthma risk in children.Methods A total of 145 children with asthma and 108 healthy controls were included.Genotyping was performed using KASP and MassARRAY SNP technologies,and serum TSLP levels were measured by ELISA.Differences in allele and genotype frequencies between the two groups were analyzed,along with the impact of genetic models on asthma risk.Differences in serum TSLP levels across groups were compared.Linkage disequilibrium and haplotype analysis were performed using Haploview 4.2,and GMDR 0.9 software was used to assess gene-environment interactions.Results No significant differences were found in the allele and genotype frequencies of the three TSLP gene loci between the two groups(P＞0.05).Under the co-dominant model,children with the AG genotype at the rs3806932 locus had 1.750 times the risk of developing asthma compared to those with the AA genotype(95％CI:1.018-3.010,P=0.043).Under co-dominant and overdominant models,children with the CT genotype at the rs11466741 locus had 1.705 times the asthma risk compared to those with the CC genotype(95％CI:1.006-2.891,P=0.048),and 1.698 times the risk compared to those with the CC-TT genotype(95％CI:1.019-2.827,P=0.041).Serum TSLP levels were significantly higher in asthma patients with the CT genotype than those with the CC genotype at the rs11466741 locus(P=0.032).Serum TSLP levels were higher in the asthma group with allergic rhinitis(AR)compared to the group without AR(P＜0.01).No significant differences were observed in the distribution of haplotypes frequencies(AC,GT,GC)between the two groups(P＞0.05).GMDR analysis showed that the highest asthma risk was observed in children with heterozygous genotypes(CT,AG)at both rs11466741 and rs2289278,or those with the CT genotype at rs11466741,a history of passive smoking,and a cesarean section delivery(P＜0.05).Conclusion Polymorphisms in the TSLP gene at rs3806932 and rs11466741 are associated with an increased risk of childhood asthma.Variants at the rs11466741 locus affect serum TSLP levels in children with asthma.Asthma combined with AR leads to elevation of serum TSLP levels.The interaction between rs11466741 and rs2289278,along with environmental factors(passive smoking and cesarean section),contributes to the increase of asthma risk in children.

Purpose To investigate the expression of LAMB3 and ITGB4 in esophageal squamous cell carcinoma(ESCC)and analyze their associations with clinicopathological features.Methods Bioinformatics was used to assess the expression of LAMB3 and ITGB4 in pan-cancer and ESCC.Immunohistochemistry was performed to evaluate their expression and distribution in ESCC tissues,and correlations clinicopathological features were analyzed.Follow-up data were collected to construct Kaplan-Meier survival curves,and Cox regression analysis was proformed to determine their prognostic significance.Results Bioinformatics analysis showed that LAMB3 and ITGB4 were highly expressed in ES-CC tissues(P＜0.001).Immunohistochemistry confirmed that both proteins were localized in the cytoplasm and membrane of tumor cells.High LAMB3 expression was significantly associated with poor differentiation(P＜0.001),lymph node metastasis(P=0.015),and T staging(P＜0.001).High ITGB4 expression was significantly correlated with poor differentiation(P=0.004)and advanced T staging(P=0.004).Cox regression analysis identified high ex-pression of LAMB3 and ITGB4 as independent prognostic factors for overall survival[HR=4.97(95％CI:2.73-9.02);HR=2.33(95％CI:1.36-3.99)].Conclusion LAMB3 and ITGB4 are highly expressed in ESCC.High LAMB3 expression is associated with tumor differentiation,lymph node metastasis,and T staging,while high ITGB4 expression is correlated with tumor differentiation and T staging.Patients with high expression of LAMB3 or ITGB4 have poorer overall survival,suggesting that these proteins may serve as prognostic biomarkers for unfavorable outcome in ESCC.

The aim of this study is to identify the cause of death of a South China tiger cub at the Meihuashan breeding institute of Fujian Province.Pathogenic bacteria were isolated and cultured from liver,spleen,lung and other tissue samples of the dead South China tiger aseptically.The iso-lated bacteria were identified through morphological observation,biochemical characterization,sequence analysis of housekeeping gene gyrB,virulence gene detection,animal pathogenicity test and drug sensitivity test.A pathogenic Aeromonas hydrophila strain,designated FJ/Tiger-201809 was successfully isolated from the trachea of dead South China tiger.The nucleotide sequence ho-mology between the isolate and 11 strains of Aeromonas gyrB ranged from 91.2％to 99.1％,with the highest homology of 99.1％observed with Aeromonas hydrophila(AF208251.1).Genetic evo-lution analysis showed that the isolated strain FJ/Tiger-201809 was in the same evolutionary branch as other reference strains of Aeromonas hydrophila and was closely related.The pathoge-nicity test in mice showed artificial infection of mice with the strain resulted in varying degrees of lesions in several organs of the mice,and the median lethal dose(LD50)was 1 × 107.8 CFU/mL.Virulence gene test results showed that the isolate FJ/Tiger-201809 carried two virulence genes,aer and act.The results of drug sensitivity test showed that FJ/Tiger-201809 was highly sensitive to enrofloxacin and ampicillin among 18 commonly used antibiotics,relatively sensitive to penicil-lin G and doxycycline,and resistant to the other 14 antibiotics.In conclusion,this study isolated and identified a strain of Aeromonas hydrophila from a dead South China tiger with multiple drug resistance and strong pathogenicity,which provided an important reference for the prevention and control of bacterial diseases in South China tiger.

Objective:To evaluate the role of NOD-like receptor protein 3 (NLRP3) inflammasome-mediated microglia activation in myocardial ischaemia-reperfusion-induced brain injury in mice.Methods:Fifty-two SPF healthy male wild-type C57BL/6 mice and 52 NLRP3 -/- mice, aged 8-10 weeks, were divided into 4 groups ( n=26 each) using a random number table method: wild type sham operation group (W-S group), wild type myocardial ischemia-reperfusion group (W-IR group), NLRP3 -/- sham operation group (NLRP3 -/--S group), and NLRP3 -/- myocardial ischemia-reperfusion group (NLRP3 -/--IR group). The myocardial ischemia-reperfusion-induced brain injury model was established by ligating the left anterior descending coronary artery for 45 min followed by 24 h of reperfusion in anesthetized mice. The cognitive function was evaluated using the modified Morris water maze test at 24 h of reperfusion. The mice were sacrificed after blood specimens were collected, and brain tissues were obtained for measurement of the blood-brain barrier permeability and water content, for microscopic examination of the pathological changes of brain tissues, and for determination of serum S-100β protein and neuron-specific enolase (NSE) concentrations, contents of interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) in hippocampal tissues (by enzyme-linked immunosorbent assay), expression of NLRP3, apoptosis-associated speck-like protein (ASC), cleaved cysteine aspartate protease 1 (cleaved-caspase-1), gasdermin D (GSDMD), ionized calcium-binding adapter molecule 1 (Iba-1), and occludin in hippocampal tissues (by immunofluorescence and/or Western blot). The apoptosis rate of neurons and density of dendritic spine were calculated. Results:Compared with sham operation group, the escape latency was significantly prolonged, the number of crossing the original platform was decreased, and the time spent in the target quadrant was shortened, the concentrations of serum S-100β protein and NSE were increased, the blood-brain barrier permeability and brain water content were increased, the dendritic spine density in the hippocampal CA1 area was decreased, the contents of IL-1β, IL-6 and TNF-α were increased, the expression of NLRP3, ASC, cleaved-caspase-1, GSDMD and Iba-1 was up-regulated, and the expression of occludin was down-regulated ( P<0.05), and the pathological injury to brain tissues was found in ischemia-reperfusion group. Compared with W-IR group, the escape latency was significantly shortened, the number of crossing the original platform was increased, and the time spent in the target quadrant was prolonged, the concentrations of serum S-100β protein and NSE were decreased, the blood-brain barrier permeability and brain water content were decreased, the dendritic spine density in the hippocampal CA1 area was increased, the contents of IL-1β, IL-6 and TNF-α were decreased, the expression of NLRP3, ASC, cleaved-caspase-1, GSDMD and Iba-1 was down-regulated, and the expression of occludin was up-regulated ( P<0.05), and the pathological injury to brain tissues was alleviated in NLRP3 -/--IR group. Conclusions:NLRP3 inflammasome-mediated microglia activation is involved in myocardial ischaemia-reperfusion-induced brain injury in mice.

Space radiation is the most important environmental harmful factor in long-term manned spaceflight and deep space exploration, and it may produce deterministic and stochastic effects on tissues and organs. In-depth research into the biological effects, mechanisms, and protective measures of space radiation is essential and serves as an important foundation for exploring radiation biology and promoting major manned space projects. Firstly, this review introduces the spatiotemporal distribution characteristics of space radiation during low-earth orbit flights, manned lunar landings, and deep space exploration missions, as well as the health risks and challenges it posed to astronauts. Then, it discusses medical requirements and exposure limits, risk assessment, and protection technologies included in the space radiation protection system established internationally and over 30 years of Chinese manned spaceflight departments. Finally, it outlines the subsequent work and prospects for further research.

Objective To evaluate the diagnostic value of positive serum specific antibodies to Mycoplasma pneumoniae(MP)in children with Mycoplasma pneumoniae pneumonia(MPP).Methods PubMed,Cochrane Library,Embase,Sinomed,CNKI,Wanfang and VIP databases were searched for studies on the detection of MPP based on antibodies from the establishment of the database to March 31,2023.After literature screening and data extraction,STATA 16.0 software was used for Meta-analysis.Results A total of 9 literatures and 2 148 clinical samples were included.The combined sensitivities[M(95%CI)]of particle agglutination assay(PA)and enzyme-linked immunosorbent assay(ELISA)were 50%(31～69)and 88%(85～90),and the combined specificities[M(95%CI)]were 88%(76～95)and 88%(62～97).The combined diagnostic odds ratio(DOR)[M(95%CI)]were 5.61(3.30～9.53)and 43.82(12.78～150.19),and the summary receiver operating characteristic curve(SROC)area under the curve(AUC)were 0.80 and 0.88,respectively.Conclusion Serum MP specific antibody detection can be used for diagnosis and screening of children MPP,but needs to be combined with clinical symptoms improve the accuracy of the diagnosis.

BACKGROUND:Protein is one of the essential nutrients for the human body and is a key component of human cell tissue.Protein supplementation can promote the synthesis of myofibrillar protein and play a key role in strength training.However,the interaction mechanism and signaling pathway between protein and exercise are still unclear.OBJECTIVE:To explore the mechanism of interaction between exercise and protein,and to optimize the benefits of protein supplementation on exercise performance.METHODS:Using"sports,proteins,amino acids,polypeptide,interaction mechanisms,signaling pathway"as Chinese and English search terms,we searched WanFang Data,CNKI,VIP,and PubMed databases respectively.Articles were screened according to the inclusion criteria,and finally 73 articles were included in the review.RESULTS AND CONCLUSION:Current research on protein supplementation promoting exercise performance mainly focuses on promoting muscle growth,endurance improvement,and body recovery through protein supplementation,but there are differences in the existing experimental results.The interaction mechanism between protein molecules and proteins in the body is not yet clear.The research on the interaction mechanism between exercise and peptides is still in its infancy.Exercise can stimulate the full absorption of external protein intake,which can affect the mechanism of protein molecules in the body.Supplementing peptide nutrition can more accurately affect the body's state,thus better eliminating the phenomena of"sub-health"and"modern diseases."Therefore,studying the interaction mechanism between exercise and proteins is particularly important,delving into the specific mechanisms by which amino acids act on the body,and further exploring the interaction mechanism between exercise and peptides.

The aim of this study is to identify the cause of death of a South China tiger cub at the Meihuashan breeding institute of Fujian Province.Pathogenic bacteria were isolated and cultured from liver,spleen,lung and other tissue samples of the dead South China tiger aseptically.The iso-lated bacteria were identified through morphological observation,biochemical characterization,sequence analysis of housekeeping gene gyrB,virulence gene detection,animal pathogenicity test and drug sensitivity test.A pathogenic Aeromonas hydrophila strain,designated FJ/Tiger-201809 was successfully isolated from the trachea of dead South China tiger.The nucleotide sequence ho-mology between the isolate and 11 strains of Aeromonas gyrB ranged from 91.2％to 99.1％,with the highest homology of 99.1％observed with Aeromonas hydrophila(AF208251.1).Genetic evo-lution analysis showed that the isolated strain FJ/Tiger-201809 was in the same evolutionary branch as other reference strains of Aeromonas hydrophila and was closely related.The pathoge-nicity test in mice showed artificial infection of mice with the strain resulted in varying degrees of lesions in several organs of the mice,and the median lethal dose(LD50)was 1 × 107.8 CFU/mL.Virulence gene test results showed that the isolate FJ/Tiger-201809 carried two virulence genes,aer and act.The results of drug sensitivity test showed that FJ/Tiger-201809 was highly sensitive to enrofloxacin and ampicillin among 18 commonly used antibiotics,relatively sensitive to penicil-lin G and doxycycline,and resistant to the other 14 antibiotics.In conclusion,this study isolated and identified a strain of Aeromonas hydrophila from a dead South China tiger with multiple drug resistance and strong pathogenicity,which provided an important reference for the prevention and control of bacterial diseases in South China tiger.

Purpose To investigate the expression of LAMB3 and ITGB4 in esophageal squamous cell carcinoma(ESCC)and analyze their associations with clinicopathological features.Methods Bioinformatics was used to assess the expression of LAMB3 and ITGB4 in pan-cancer and ESCC.Immunohistochemistry was performed to evaluate their expression and distribution in ESCC tissues,and correlations clinicopathological features were analyzed.Follow-up data were collected to construct Kaplan-Meier survival curves,and Cox regression analysis was proformed to determine their prognostic significance.Results Bioinformatics analysis showed that LAMB3 and ITGB4 were highly expressed in ES-CC tissues(P＜0.001).Immunohistochemistry confirmed that both proteins were localized in the cytoplasm and membrane of tumor cells.High LAMB3 expression was significantly associated with poor differentiation(P＜0.001),lymph node metastasis(P=0.015),and T staging(P＜0.001).High ITGB4 expression was significantly correlated with poor differentiation(P=0.004)and advanced T staging(P=0.004).Cox regression analysis identified high ex-pression of LAMB3 and ITGB4 as independent prognostic factors for overall survival[HR=4.97(95％CI:2.73-9.02);HR=2.33(95％CI:1.36-3.99)].Conclusion LAMB3 and ITGB4 are highly expressed in ESCC.High LAMB3 expression is associated with tumor differentiation,lymph node metastasis,and T staging,while high ITGB4 expression is correlated with tumor differentiation and T staging.Patients with high expression of LAMB3 or ITGB4 have poorer overall survival,suggesting that these proteins may serve as prognostic biomarkers for unfavorable outcome in ESCC.