1.Development of a microfluidic chip-based in vitro model of retinal microvasculature and thrombosis therein
Shuxian SHAO ; Yanmei WANG ; Yihan XU ; Jiaxin ZHENG ; Yufan ZHANG ; Danning LIU ; Yuan LI
Journal of Army Medical University 2025;47(11):1199-1207
Objective To develop an endothelialized microfluidic chip model that simulates the spatial architecture and bioactivity of retinal vasculature,enabling thrombosis modeling and thrombolytic efficacy validation.Methods A tri-level microvascular network chip(300/200/100 μm diameters)with bifurcated architecture was fabricated using soft lithography.Human retinal microvascular endothelial cells(HRMECs)were perfused into channels,with endothelial coverage monitored via phase-contrast microscopy and F-actin staining.Cellular bioactivity was assessed using mitochondrial membrane potential probes(5,5,6,6-Tetrachloro-1,1,3,3-tetraethylbenzimidazolylcarbocyanine iodide,JC-1)and nitric oxide(NO)quantification.Fresh blood samples from 10 healthy donors(Yongchuan Hospital Affiliated to Chongqing Medical University,March to June 2024)were perfused with digital injection pump to mimic blood flow in human body into 3 experimental groups:normal whole blood,and TNF-α-activated endothelium+normal blood,TNF-α-activated endothelium+TNF-α-treated blood.Three inlet blood flow rates of 37.8、11.1 and 3.5 μL/min were set in each group.Two experimental groups,normal saline and recombinant human tissue-type plasminogen activator(rtPA),were established using the endothelialized microfluidic thrombosis model to validate thrombolytic efficacy.Endothelial functional impacts were assessed through integrated DAPI/NO staining and thrombosis model analysis across 3 intervention phases:pre-thrombosis,post-thrombosis,and post-thrombolysis.Results A tri-level microfluidic vascular model(300/200/100 μm diameters)was successfully constructed.In 72 h after endothelial cell perfusion,complete channel coverage was achieved,with phase-contrast microscopy and F-actin staining confirming confluent cellular alignment.JC-1/NO assays validated preserved endothelial bioactivity.Compared with the whole blood group,both TNF-α-activated endothelium+normal blood and TNF-α-activated endothelium+TNF-α-treated blood groups exhibited significantly increased thrombus occupancy rates at identical flow rates(all P<0.001).Notably,TNF-α-activated endothelium+TNF-α-treated blood group demonstrated the highest thrombus ratio at 3.5 μL/min(P<0.001).The rtPA group showed superior thrombolytic efficacy versus saline(P<0.001).Endothelial monolayer integrity was maintained across intervention phases,with thrombosis triggering significant NO elevation(P<0.001).Conclusion Our retinal vasculature-mimetic microfluidic model enables precise thrombosis modeling and drug evaluation,providing new methodology for studying retinal vascular occlusive diseases.
2.Application value of neck circumference in screening for overweight and obesity among children and adolescents
LIU Fang, YUAN Shuxian, LI Yuan, HAO Huimin, LIN Yifan, CHEN Yongxing, WEI Haiyan
Chinese Journal of School Health 2024;45(7):1040-1044
Objective:
To discuss the clinical value of neck circumference in screening for overweight and obesity in children and adolescents, so as to provide a theoretical basis and new ideas for overweight and obesity screening.
Methods:
From May to July 2023, a total of 2 493 children and adolescents aged 3 to 16 were sampled from three schools by the cluster random sampling method. General data, neck circumference, body mass index (BMI), waisttoheight ratio, and other information were collected. Mann-Whitney ranksum test, Spearman correlation analysis, and receiver operating characteristic (ROC) curve analysis were used to statistically analyze the data.
Results:
The prevalence of overweight and obesity in children and adolescents aged 3 to 16 was 33.05%, and the prevalence of abdominal obesity was 28.33%.The neck circumferences of boys and girls in the overweight and obese group showed statistically significant differences from the normal weight group during the preschool, schoolage, and adolescence periods (Z=-16.69--4.54, P<0.05). The neck circumferences of children of different genders were moderately positively correlated with BMI (r=0.50-0.79, P<0.01). ROC curve analysis showed that neck circumference had good accuracy in assisting the screening for the occurrence of overweight and obesity in boys and girls during the preschool, schoolage, and adolescence periods [the AUC for boys:0.80(0.71-0.89), 0.89(0.86-0.91), 0.84(0.81-0.87); the AUC for girls:0.76(0.67-0.86), 0.81(0.74-0.88), 0.73(0.68-0.77), P<0.01], the optimal neck circumference cutoff values for boys were 26.95, 28.95, 33.55 cm, and for girls were 25.05, 26.55, 28.35 cm respectively. The neck circumferences of boys and girls were moderately positively correlated with the waisttoheight ratio during the schoolage and adolescence periods (r=0.41-0.70, P<0.01). ROC curves showed that neck circumferences had good accuracy in assisting the screening for the occurrence of abdominal obesity in boys and girls during the schoolage and adolescence periods [the AUC for boys:0.89(0.86-0.92), 0.82(0.78-0.85); the AUC for girls:0.84(0.75-0.93), 0.87(0.75-0.93)], the optimal cutoff values for boys were 28.95, 32.75 cm; for girls were 26.45, 31.85 cm respectively.
Conclusion
The neck circumference can be applied to screen for overweight and abdominal obesity in children and adolescents, and can provide new ideas for the prevention and control of overweight and obesity in children and adolescents.
3.Application of serum tumor specific protein 70 for prognostic stratification in acute myeloid leukemia
Yiling HUANG ; Fei JIN ; Lixia ZHANG ; Yuan MU ; Fengyun LU ; Wenying XIA ; Qiong ZHU ; Shuxian YANG ; Jian XU ; Shiyang PAN
Chinese Journal of Preventive Medicine 2024;58(10):1541-1547
Objective:To assess the value of serum tumor specific protein 70 (SP70) for prognostic stratification in acute myeloid leukemia (AML).Methods:A cohort study design was adopted. 129 newly diagnosed AML patients from September 2022 to January 2024 at the Hematology Department of the First Affiliated Hospital of Nanjing Medical University were included, as well as a control group consisted of 120 healthy individuals and 7 cases with benign hematologic diseases during the same period (total 127 cases). Clinical data were collected from Electronic Medical Records. According to the 2023 edition of the Chinese Leukemia Diagnosis and Treatment Guidelines, AML patients with good or moderate prognosis were categorized as low-to-intermediate risk, while those with poor prognosis were high-risk group. Univariate and multivariate logistic regression analyses were used to identify variables significantly associated with AML prognostic risk. ROC analysis was used to evaluate diagnostic performance. A nomogram for predicting patient prognostic risk was constructed by R 4.0.2 software, and the internal validation was performed using bootstrapping.Results:Among 129 AML patients, there were 71 males (55.0%) and 58 females (45.0%), with 42 (32.6%) classified as high-risk and 87 (67.4%) as low-intermediate risk. The high-risk group had a significantly higher median age [62 (48, 67) years] compared to the low-intermediate risk group [50 (35, 63) years, Z=-2.381, P=0.017], and a significantly higher proportion of males (30 patients, 71.4%) compared to the low-intermediate risk group (41 patients, 47.1%, χ 2=6.760, P=0.009). Multivariate logistic regression analysis indicated that serum SP70 ( OR=2.54, 95% CI: 1.68-3.84, P<0.001), hemoglobin (HB) ( OR=0.96, 95% CI: 0.93-0.99, P<0.05), and bone marrow blast (BM blast) ( OR=1.07, 95% CI: 1.02-1.13, P<0.05) were independent risk factors for high-risk prognosis in AML patients. ROC analysis showed that the area under the curve (AUC) for SP70 predicting high-risk patients was 0.908 (cut-off value of 5.74 ng/ml, 95% CI: 0.845-0.952, sensitivity 90.5%, specificity 82.8%). The combined model of serum SP70, HB, and BM blasts had an AUC of 0.931 (95% CI: 0.890-0.973); C-index=0.925 (95% CI: 0.876-0.963),with no statistically significant difference compared to serum SP70 alone ( Z=1.693, P>0.05). Conclusion:Serum SP70 may be a promising non-invasive molecular biomarker for prognostic stratification in AML.
4.Application of serum tumor specific protein 70 for prognostic stratification in acute myeloid leukemia
Yiling HUANG ; Fei JIN ; Lixia ZHANG ; Yuan MU ; Fengyun LU ; Wenying XIA ; Qiong ZHU ; Shuxian YANG ; Jian XU ; Shiyang PAN
Chinese Journal of Preventive Medicine 2024;58(10):1541-1547
Objective:To assess the value of serum tumor specific protein 70 (SP70) for prognostic stratification in acute myeloid leukemia (AML).Methods:A cohort study design was adopted. 129 newly diagnosed AML patients from September 2022 to January 2024 at the Hematology Department of the First Affiliated Hospital of Nanjing Medical University were included, as well as a control group consisted of 120 healthy individuals and 7 cases with benign hematologic diseases during the same period (total 127 cases). Clinical data were collected from Electronic Medical Records. According to the 2023 edition of the Chinese Leukemia Diagnosis and Treatment Guidelines, AML patients with good or moderate prognosis were categorized as low-to-intermediate risk, while those with poor prognosis were high-risk group. Univariate and multivariate logistic regression analyses were used to identify variables significantly associated with AML prognostic risk. ROC analysis was used to evaluate diagnostic performance. A nomogram for predicting patient prognostic risk was constructed by R 4.0.2 software, and the internal validation was performed using bootstrapping.Results:Among 129 AML patients, there were 71 males (55.0%) and 58 females (45.0%), with 42 (32.6%) classified as high-risk and 87 (67.4%) as low-intermediate risk. The high-risk group had a significantly higher median age [62 (48, 67) years] compared to the low-intermediate risk group [50 (35, 63) years, Z=-2.381, P=0.017], and a significantly higher proportion of males (30 patients, 71.4%) compared to the low-intermediate risk group (41 patients, 47.1%, χ 2=6.760, P=0.009). Multivariate logistic regression analysis indicated that serum SP70 ( OR=2.54, 95% CI: 1.68-3.84, P<0.001), hemoglobin (HB) ( OR=0.96, 95% CI: 0.93-0.99, P<0.05), and bone marrow blast (BM blast) ( OR=1.07, 95% CI: 1.02-1.13, P<0.05) were independent risk factors for high-risk prognosis in AML patients. ROC analysis showed that the area under the curve (AUC) for SP70 predicting high-risk patients was 0.908 (cut-off value of 5.74 ng/ml, 95% CI: 0.845-0.952, sensitivity 90.5%, specificity 82.8%). The combined model of serum SP70, HB, and BM blasts had an AUC of 0.931 (95% CI: 0.890-0.973); C-index=0.925 (95% CI: 0.876-0.963),with no statistically significant difference compared to serum SP70 alone ( Z=1.693, P>0.05). Conclusion:Serum SP70 may be a promising non-invasive molecular biomarker for prognostic stratification in AML.
5.Clinical analysis of neuropsychological characteristics in adolescents with Turner syndrome
Xiaojing LIU ; Huimin HAO ; Jing GAO ; Shuxian YUAN ; Suhua LIU ; Yongxing CHEN ; Minli DING ; Qiujin QIAN ; Haiyan WEI
Chinese Journal of Applied Clinical Pediatrics 2024;39(11):858-861
Objective:To analyze the neurocognitive abnormalities and related emotional and behavioral problems in 410 adolescent patients with Turner syndrome (TS) managed in Henan Children′s Hospital in the past 5 years, and to explore the relationship between neurocognitive abnormalities and chromosome karyotype, pubertal development, hormone replacement therapy.Methods:A retrospective case series study.A total of 410 adolescent patients who were diagnosed with TS by karyotype or fluorescence in situ hybridization in the outpatient or inpatient Department of Endocrinology, Genetics and Metabolism at Henan Children′s Hospital from June 2018 to June 2023 were selected and divided into 2 groups according to age: < 12 years old and 12-18 years old.Neurocognitive assessments were performed based on the results of the Wechsler Intelligence Scale (4 th edition) for children and behavior scales for children, SPSS 22.0 software was used for data processing and statistical analysis, and chi-square test was used to analyze the correlation between chromosome karyotype, intelligence development level, pubertal development status, hormone therapy status and the occurrence of neuropsychiatric diseases. Results:Among the 410 TS patients, 207 cases had the karyotype of 45, X0/46, XX, accounting for 50.49%, 94 cases had the monosomic karyotype of 45, X0, accounting for 22.93%.Forty-six patients completed the Wechsler intelligence test, with the intelligence quotient (IQ) score ranging from 70 to 105, with high verbal comprehension and perceptual reasoning scores and low processing speed and working memory scores on all assessments.Fifty-two patients completed the hyperactivity scale assessment, and 43 cases had a predisposition to attention deficit hyperactivity disorder (ADHD).There were no significant differences in total IQ, perceptual reasoning and processing speed among the children with karyotype 45, X0, chimeric, and X chromosome structural abnormalities ( H=3.161, 1.955, 5.890, all P>0.05), while there were significant differences in verbal comprehension and working memory among the three groups ( H=7.697, 9.694, all P<0.05).Among TS patients 12-18 years old, 68 cases completed the depression scale self-assessment, of which 23 cases had depressive tendencies.There was no correlation between depressive tendency and chromosome karyotype, pubertal development and hormone replacement therapy ( P>0.05). Conclusions:TS patients generally have low intelligence levels and tend to have ADHD in childhood.TS patients in the pubertal development have a high incidence of depression.Pubertal development status and hormone replacement therapy show no correlation with the occurrence of neuropsychiatric diseases in TS patients.
6.Value of the serum levels of Clusterin and sphingosine 1-phosphate in assessing the prognosis of sepsis patients with acute liver injury
Dazhou XU ; Shuxian ZHANG ; Kun WANG ; Chenyan ZUO ; Yi ZENG ; Qingwen YUAN ; Zhimei ZHANG
Journal of Clinical Hepatology 2023;39(12):2867-2872
ObjectiveTo investigate the value of the serum levels of Clusterin and sphingosine 1-phosphate (S1P) in assessing the prognosis of sepsis patients with acute liver injury. MethodsA total of 127 sepsis patients with acute liver injury who were admitted to Lianyungang Hospital, Xuzhou Medical University, from March 2019 to May 2022 were enrolled, and according to their prognosis after 28 days of treatment, they were divided into death group with 35 patients and survival group with 92 patients. The independent-samples t test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between groups. A pearson correlation analysis was used to investigate the correlation. The prognostic value of serum Clusterin and S1P was analyzed by receiver operating characteristic curve. ResultsThere were significant differences between the two groups in the degree of liver injury, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHEⅡ) score, Sequential Organ Failure Assessment (SOFA) score, the presence or absence of acute kidney injury, prothrombin time (PT), international normalized ratio (INR), Child-Pugh class, and C-reactive protein (all P<0.05). The death group had significantly lower serum levels of Clusterin and S1P than the survival group (t=11.094 and 10.390, both P<0.05). The patients with severe liver injury had significantly lower serum levels of Clusterin and S1P than those with mild or moderate liver injury (t=9.825 and 11.418, both P<0.05). The multivariate regression analysis showed that the degree of liver injury (odds ratio [OR]=1.260, 95% confidence interval [CI]: 1.081 — 1.468, P<0.05), APACHEII score (OR=1.031, 95%CI: 1.019 — 1.044, P<0.05), SOFA score (OR=1.066, 95%CI: 1.039 — 1.094, P<0.05), Clusterin (OR=0.899, 95%CI: 0.859 — 0.940, P<0.05), and S1P (OR=0.824, 95%CI: 0.749 — 0.908, P<0.05) were independent risk factors for the prognosis of patients with sepsis. The ROC curve analysis showed that serum Clusterin and S1P used alone or in combination had an area under the ROC curve of 0.864, 0.861, and 0.949, respectively. Serum Clusterin and S1P were significantly negatively correlated with alanine aminotransferase, total bilirubin, PT, and INR in sepsis patients with acute liver injury (all P<0.05). ConclusionThe sepsis patients with acute liver injury who died had significant reductions in serum Clusterin and S1P compared with those who survived, and the levels of Clusterin and S1P are closely associated with the degree of liver injury. The combination of Clusterin and S1P has a good value in predicting the prognosis of sepsis patients with acute liver injury and is expected to become a potential marker for predicting the prognosis of sepsis patients with acute liver injury.
7.Genetic analysis of a case with 11β hydroxylase deficiency caused by CYP11B2/CYP11B1 chimeric gene.
Yifan LIN ; Haihua YANG ; Shuxian YUAN ; Dongxiao LI ; Haiyan WEI ; Xiaocui MA
Chinese Journal of Medical Genetics 2023;40(4):462-467
OBJECTIVE:
To analyze a child with 11β hydroxylase deficiency (11β-OHD) due to CYP11B2/CYP11B1 chimeric gene.
METHODS:
Clinical data of the child who was admitted to Henan Children's Hospital on August 24, 2020 were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RT-PCR and Long-PCR were carried out to verify the presence of chimeric gene.
RESULTS:
The patient, a 5-year-old male, had featured premature development of secondary sex characteristics and accelerated growth, and was diagnosed with 21 hydroxylase deficiency (21-OHD). WES revealed that he has harbored a heterozygous c.1385T>C (p.L462P) variant of the CYP11B1 gene, in addition to a 37.02 kb deletion on 8q24.3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1385T>C (p.L462P) was rated as a likely pathogenic variant (PM2_Supporting+PP3_Moderate+PM3+PP4). The results of RT-PCR and Long-PCR suggested that CYP11B1 and CYP11B2 genes have recombined to form a CYP11B2 exon 1~7/CYP11B1 exon 7~9 chimeric gene. The patient was diagnosed as 11β-OHD and effectively treated with hydrocortisone and triptorelin. A healthy fetus was delivered following genetic counseling and prenatal diagnosis.
CONCLUSION
11β-OHD may be misdiagnosed as 21-OHD due to the potential CYP11B2/CYP11B1 chimeric gene, which will require multiple methods for the detection.
Child, Preschool
;
Humans
;
Male
;
Adrenal Hyperplasia, Congenital/genetics*
;
Cytochrome P-450 CYP11B2/genetics*
;
Exons
;
Retrospective Studies
;
Steroid 11-beta-Hydroxylase/genetics*
8.Medical Institution's Multiple Role in the Collaborative Innovation Transformation Mode of "Industry-University-Research-Medicine" on Domestic Surgical Robots.
Zhiqun SHU ; Jialu QU ; Shuxian ZHANG ; Yirou TIE ; Yuan CHE ; Junting LI ; Letong JIANG ; Huiqing SHEN
Chinese Journal of Medical Instrumentation 2023;47(5):582-586
In recent years, with the rapid development of Chinese domestic surgical robot technology and the expansion of the application market, the "industry-university-research-medicine" collaborative innovation transformation mode has gradually developed and formed. Medical institutions play an important role in multi-party cooperation with enterprises, universities, and research institutes, as well as in product planning, technology research and development, achievement transformation, and personnel training. On the basis of reviewing the current situation of the development of the "industry-university-research-medicine" collaborative innovation transformation mode of domestic surgical robots, this study explores the multiple roles played by medical institutions in this mode and challenges, further putting forward corresponding recommendations.
Humans
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Robotics
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Universities
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Medicine
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Industry
;
Technology
9.Role of Histone Modifications in Acute Kidney Injury Progressing to Chronic Kidney Disease
Shuxian GUO ; Zeyang ZHANG ; Jin ZHAO ; Jinguo YUAN ; Shiren SUN
Journal of Sichuan University (Medical Sciences) 2023;54(6):1080-1084
Acute kidney injury(AKI),a clinical syndrome caused by various factors,is characterized by a rapid decline in kidney function in a short period of time.AKI affects the short-term prognosis of patients and may also induce chronic kidney disease(CKD).However,the current treatment options for AKI mainly focus on symptom management.Specific therapeutic measures available for the prevention of transition from AKI to CKD are very limited in number.Histones are basic proteins that intricately bind the DNA in chromosomes.After translation,histones undergo various modifications on their amino-terminal tails,such as methylation,acetylation,phosphorylation,ubiquitination,and lactylation,collectively forming the"histone code",which affects the expression of genes mainly by regulating the elastic structure of chromatin or recruiting specific proteins.Extensive research conducted in recent years on histone post-translational modifications(PTMs)has also sparked continuous interest in their association with the AKI-to-CKD transition.Therefore,this paper highlights the significant role of PTMs in the process of AKI developing and progressing to CKD,with a view to finding new approaches to preventing the progression of AKI to CKD.
10.A Novel Anti-Microbial Peptide from Pseudomonas, REDLK Induced Growth Inhibition of Leishmania tarentolae Promastigote In Vitro
Yanhui YU ; Panpan ZHAO ; Lili CAO ; Pengtao GONG ; Shuxian YUAN ; Xinhua YAO ; Yanbing GUO ; Hang DONG ; Weina JIANG
The Korean Journal of Parasitology 2020;58(2):173-179
Leishmaniasis is a prevalent cause of death and animal morbidity in underdeveloped countries of endemic area. However, there is few vaccine and effective drugs. Antimicrobial peptides are involved in the innate immune response in many organisms and are being developed as novel drugs against parasitic infections. In the present study, we synthesized a 5-amino acid peptide REDLK, which mutated the C-terminus of Pseudomonas exotoxin, to identify its effect on the Leishmania tarentolae. Promastigotes were incubated with different concentration of REDLK peptide, and the viability of parasite was assessed using MTT and Trypan blue dye. Morphologic damage of Leishmania was analyzed by light and electron microscopy. Cellular apoptosis was observed using the annexin V-FITC/PI apoptosis detection kit, mitochondrial membrane potential assay kit and flow cytometry. Our results showed that Leishmania tarentolae was susceptible to REDLK in a dose-dependent manner, disrupt the surface membrane integrity and caused parasite apoptosis. In our study, we demonstrated the leishmanicidal activity of an antimicrobial peptide REDLK from Pseudomonas aeruginosa against Leishmania tarentolae in vitro and present a foundation for further research of anti-leishmanial drugs.


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