Objective: To prepare the erythrocyte-liposome drug delivery system to enhance the therapeutic effect of drugs on tumors and inhibit tumor metastasis. Methods: This study prepared and characterized paclitaxel (PTX)-plerixafor (AMD3100) liposomes (Lips), developed the erythrocyte-liposome drug delivery system, and evaluated its targeting efficiency and therapeutic efficacy through a series of in vitro cellular and in vivo animal experiments. Results: The particle size of PTX-AMD-Lips was (186.4±0.83) nm. Drug encapsulation efficiency of PTX-AMD-Lips was (75.50±5.27)% for PTX and (88.31±2.45)% for AMD. The Binding efficiency between RBC and liposomes in the drug delivery system was (69.93±2.55)%. Vitro cellular experiments revealed that PTX-AMD-Lips significantly inhibited tumor cell migration. In vivo animal experiments, the erythrocyte-liposome drug delivery system significantly increased drug accumulation in the lungs. At the experimental endpoint, the quantitative fluorescence signal of tumor size measured (4.04±0.44)×10 for the PTX-Lips group, and (5.14±3.40)×10 for the RBC-PTX-AMD-Lips group. Conclusion: The erythrocyte-liposome drug delivery system could enhance the lung-specific targeting capability of liposomes, kill tumor cells and suppress further metastasis effectively.

Objective:To investigate the expression pattern of pan-TRK protein in colorectal cancers with NTRK gene fusion and mismatch repair deficient (dMMR) and to analyze its molecular pathological characteristics.Methods:A total of 117 dMMR colorectal cancers diagnosed in the Department of Pathology of Henan Provincial People′s Hospital, Zhengzhou, China from 2020 to 2023 were collected. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and DNA/RNA-based next-generation sequencing (NGS) were used to detect pan-TRK protein expression and fusion partner genes in tumors, and to further explore the correlation between pan-TRK staining patterns and partner genes.Results:IHC and FISH were performed successfully in formalin-fixed paraffin-embedded tissues from 117 dMMR colorectal cancer patients. There were 15 (15/117, 12.8%) cases with positive pan-TRK, including 6 cases with strong staining in tumor cell membrane and cytoplasm, 2 cases with weakly granular staining in tumor cytoplasm, 2 cases with moderate dot-like staining in near 5% tumor cell nuclei, 1 case with moderately to strongly granular staining in the cytoplasm and membrane of tumor cells, 1 case with moderately to weakly granular staining in about 60% of the tumor cells, 1 case with strongly staining in about 1% of the tumor cells, 1 case with moderately to strongly staining in about 3% of the tumor cells and 1 case with diffuse, moderate para-nuclear dot-like and weakly perinuclear granular staining. NTRK1 gene disruption was detected in 6 cases (6/117, 5.1%) and consistent with diffusely strong expression of pan-TRK. Based on DNA/RNA NGS, it was further confirmed that the 6 cases with NTRK1 gene disruption all carried TPM3-NTRK1 fusion gene, and all had high microsatellite instability and high tumor mutation burden. No KRAS, NRAS, BRAF V600E or TP53 gene mutations were detected. Four patients carried frame shift mutations in RNF43. Other molecular changes included 3 cases with ROS1 gene mutation, 2 cases with BRAC, ALK, and EGFR gene mutations, 2 cases with ATM gene mutation, and 2 cases with KIT gene mutation. These were missense/frame shift mutations that were associated with no clinical significance. The nine pan-TRK-positive cases without NTRK gene fusion detected with DNA-based NGS were further confirmed with RNA-based NGS, and no NTRK gene fusion was found. The sensitivity and specificity of NTRK gene fusion detected using IHC were 100.0% and 92.5%, respectively. The sensitivity and specificity of diffusely strong membranous/cytoplasmic staining were both 100.0%.Conclusions:Pan-TRK protein has various expression patterns in dMMR colorectal cancer. Its diffusely strong expression is highly suggestive of NTRK1 gene fusion. TPM3-NTRK1 gene fusion is a common form of NTRK gene fusion in dMMR colorectal cancer.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective:To investigate the expression pattern of pan-TRK protein in colorectal cancers with NTRK gene fusion and mismatch repair deficient (dMMR) and to analyze its molecular pathological characteristics.Methods:A total of 117 dMMR colorectal cancers diagnosed in the Department of Pathology of Henan Provincial People′s Hospital, Zhengzhou, China from 2020 to 2023 were collected. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and DNA/RNA-based next-generation sequencing (NGS) were used to detect pan-TRK protein expression and fusion partner genes in tumors, and to further explore the correlation between pan-TRK staining patterns and partner genes.Results:IHC and FISH were performed successfully in formalin-fixed paraffin-embedded tissues from 117 dMMR colorectal cancer patients. There were 15 (15/117, 12.8%) cases with positive pan-TRK, including 6 cases with strong staining in tumor cell membrane and cytoplasm, 2 cases with weakly granular staining in tumor cytoplasm, 2 cases with moderate dot-like staining in near 5% tumor cell nuclei, 1 case with moderately to strongly granular staining in the cytoplasm and membrane of tumor cells, 1 case with moderately to weakly granular staining in about 60% of the tumor cells, 1 case with strongly staining in about 1% of the tumor cells, 1 case with moderately to strongly staining in about 3% of the tumor cells and 1 case with diffuse, moderate para-nuclear dot-like and weakly perinuclear granular staining. NTRK1 gene disruption was detected in 6 cases (6/117, 5.1%) and consistent with diffusely strong expression of pan-TRK. Based on DNA/RNA NGS, it was further confirmed that the 6 cases with NTRK1 gene disruption all carried TPM3-NTRK1 fusion gene, and all had high microsatellite instability and high tumor mutation burden. No KRAS, NRAS, BRAF V600E or TP53 gene mutations were detected. Four patients carried frame shift mutations in RNF43. Other molecular changes included 3 cases with ROS1 gene mutation, 2 cases with BRAC, ALK, and EGFR gene mutations, 2 cases with ATM gene mutation, and 2 cases with KIT gene mutation. These were missense/frame shift mutations that were associated with no clinical significance. The nine pan-TRK-positive cases without NTRK gene fusion detected with DNA-based NGS were further confirmed with RNA-based NGS, and no NTRK gene fusion was found. The sensitivity and specificity of NTRK gene fusion detected using IHC were 100.0% and 92.5%, respectively. The sensitivity and specificity of diffusely strong membranous/cytoplasmic staining were both 100.0%.Conclusions:Pan-TRK protein has various expression patterns in dMMR colorectal cancer. Its diffusely strong expression is highly suggestive of NTRK1 gene fusion. TPM3-NTRK1 gene fusion is a common form of NTRK gene fusion in dMMR colorectal cancer.

This study was aimed at determining the molecular characteristics of Yersinia pestis in the natural plague foci around Qinghai Lake through single nucleotide polymorphism technology,to lay a foundation for molecular epidemiological and source-tracing analysis of Y.pestis in this area.Using the whole genome sequencing technology,we obtained the whole genome sequences of 84 representative Y.pestis strains.Using the sequences of Y.pestis and Yersinia pseudotuberculosis IP32953 from the NCBI database as references,we compared and analyzed the 2 298 SNP loci of these strains.From 1957 to 2020,84 representative strains of Y.pestis from the natural plague foci around Qinghai Lake were divided into two clades:1.IN2 and 3.ANT1.The 1.IN2 clade was the characteristic population of Y.pestis throughout all epidemic years in this area.Additionally,analysis of the SNP distribution and hosts in the region indicated that the 1.IN2 clade was located in five counties except Wulan,whereas the 3.ANT1 clade was isolated from Himalayan marmot and dog in two counties.In conclusion,the population structure of SNP of Y.pestis in the natural plague foci around Qinghai Lake is relatively simple,and SNP analysis of Y.pestis provided a scientific basis for tracing plague epidemic sources and formulating plague prevention and control measures in this area.

Hypoxic-ischemic brain damage (HIBD) is one of the main causes of disability in middle-aged and elderly people, as well as high mortality rates and long-term physical impairments in newborns. The pathological manifestations of HIBD include neuronal damage and loss of myelin sheaths. Tau protein is an important microtubule-associated protein in brain, exists in neurons and oligodendrocytes, and regulates various cellular activities such as cell differentiation and maturation, axonal transport, and maintenance of cellular cytoskeleton structure. Phosphorylation is a common chemical modification of Tau. In physiological condition, it maintains normal cell cytoskeleton and biological functions by regulating Tau structure and function. In pathological conditions, it leads to abnormal Tau phosphorylation and influences its structure and functions, resulting in Tauopathies. Studies have shown that brain hypoxia-ischemia could cause abnormal alteration in Tau phosphorylation, then participating in the pathological process of HIBD. Meanwhile, brain hypoxia-ischemia can induce oxidative stress and inflammation, and multiple Tau protein kinases are activated and involved in Tau abnormal phosphorylation. Therefore, exploring specific molecular mechanisms by which HIBD activates Tau protein kinases, and elucidating their relationship with abnormal Tau phosphorylation are crucial for future researches on HIBD related treatments. This review aims to focus on the mechanisms of the role of Tau phosphorylation in HIBD, and the potential relationships between Tau protein kinases and Tau phosphorylation, providing a basis for intervention and treatment of HIBD.
Humans ; tau Proteins/physiology* ; Phosphorylation ; Hypoxia-Ischemia, Brain/physiopathology* ; Animals ; Oxidative Stress

Objective: To analyze the correlation between the levels of vitamin A, vitamin D, vitamin E with body fat mass percentage(FMP) as well as lifestyle factors among primary school students, so as to provide references for exploring the vitamin nutritional status of primary school students and its potential influencing factors. Methods: From September 1 to October 30, 2021, a cluster sampling method was used to select 750 thirdgrade students from eight primary schools in Luohu District, Shenzhen. Their body composition was measured, and blood samples were collected to detect the serum levels of vitamin A, vitamin D, and vitamin E using a mass spectrometer. Dietary and exercise habits were collected through questionnaires. Mann-Whitney U test and Kruskal-Wallis H rank sum test were used for inter group comparisons, spearman correlation was used for correlation analysis,and Logistic regression model was used to analyze the association between lifestyle and vitamin content. Results: The overall level of vitamin A in school aged children was 0.4 (0.4, 0.5) mg/L, with a deficiency rate of 0 and a marginal deficiency rate of 5.1%; the level of vitamin D was 26.0 (22.0, 30.0) ng/mL, with a deficiency rate of 0.4% and an insufficiency rate of 12.7%; the content of vitamin E was 11.8 (10.1, 13.5) mg/L, with an insufficiency rate of 0.8%. Spearman correlation analysis showed that vitamin A was positively correlated with FMP in the total population, boys, girls, and normal weight population ( r =0.18, 0.18, 0.20, 0.10), and vitamin D was positively correlated with FMP in the total population and obese population ( r =0.08,0.16)(all P <0.05). Logistic regression analysis showed that marginal deficiency of vitamin A was associated with consumption of animal, snack, and dairy/egg/bean foods ( OR =0.45, 0.55, 0.59); whether vitamin D was deficient was influenced by gender ( OR =2.65) and exercise ( OR = 1.96 ) (all P <0.05). Conclusion Vitamin A, vitamin D and vitamin E levels are associated with body fat percentage, with significant variations in vitamin status among individuals of different body types, necessitating targeted supplementation.

This study was aimed at determining the molecular characteristics of Yersinia pestis in the natural plague foci around Qinghai Lake through single nucleotide polymorphism technology,to lay a foundation for molecular epidemiological and source-tracing analysis of Y.pestis in this area.Using the whole genome sequencing technology,we obtained the whole genome sequences of 84 representative Y.pestis strains.Using the sequences of Y.pestis and Yersinia pseudotuberculosis IP32953 from the NCBI database as references,we compared and analyzed the 2 298 SNP loci of these strains.From 1957 to 2020,84 representative strains of Y.pestis from the natural plague foci around Qinghai Lake were divided into two clades:1.IN2 and 3.ANT1.The 1.IN2 clade was the characteristic population of Y.pestis throughout all epidemic years in this area.Additionally,analysis of the SNP distribution and hosts in the region indicated that the 1.IN2 clade was located in five counties except Wulan,whereas the 3.ANT1 clade was isolated from Himalayan marmot and dog in two counties.In conclusion,the population structure of SNP of Y.pestis in the natural plague foci around Qinghai Lake is relatively simple,and SNP analysis of Y.pestis provided a scientific basis for tracing plague epidemic sources and formulating plague prevention and control measures in this area.

Genitourinary tract infections caused by Chlamydia trachomatis ( Ct) are characterized by their insidious onset, mild symptoms, and prolonged disease course, making them challenging to treat effectively. Chronic persistent infections and associated complications impose a significant burden on both patients and society. Numerous studies have shown that relying solely on antibiotics as first-line therapy may not be sufficient to completely eradicate urogenital Ct infections. Additionally, antibiotic use can lead to the development of Ct resistance and disrupt the body′s microbial balance. Therefore, the development of novel Ct inhibitors is crucial. This review summarizes recent advances in research on Ct inhibitors, aiming to provide a valuable reference for both basic research and clinical treatment of urogenital Ct infections.