OBJECTIVES: To develop an E-selectin-targeting nanomedicine delivery system that competitively inhibits E-selectin-neutrophil ligand binding to block neutrophil adhesion to vessels and suppress their recruitment to the lesion sites. METHODS: Doxorubicin hydrochloride (DOX)-loaded liposomes (IEL-Lip/DOX) conjugated with E-selectin-affinity peptide IELLQARC were developed using a post-insertion method. Two formulations [2-1P: Mol(PC): Mol(DPI)=100:1; 2-3P: 100:3] were prepared and their modification density and in vitro release characteristics were determined. Their targeting efficacy was assessed in a cell model of LPS-induced inflammation, a mouse model of acute lung injury (ALI), a rat femoral artery model of physical injury-induced inflammation, and a zebrafish model of local inflammation. RESULTS: The prepared IEL-Lip/DOX 2-1P and 2-3P had peptide modification densities of 4.76 and 7.57 pmoL/cm², respectively. Compared with unmodified liposomes, IEL-Lip/DOX exhibited significantly reduced 48-h cumulative release rates at pH 5.5. In the inflammation cell model, IEL-Lip/DOX showed increased uptake by activated inflammatory endothelial cells, and 2-1P exhibited a higher trans-endothelial ability. In ALI mice, the fluorescence intensity of IEL-Lip/Cy5.5 increased significantly in lung tissues by 53.71% [Z-(2-1P)] and 93.41% [Z-(2-3P)], and 2-1P had an increased distribution by 24.19% in the inflammatory lung tissue compared to normal mouse lung tissue. In rat femoral artery models, 2-1P had greater injured/normal vessel fluorescence intensity contrast. In the zebrafish models, both 2-1P and 2-3P showed increased aggregation at the site of inflammation. CONCLUSIONS This E-selectin-targeting nanomedicine delivery system efficiently targets activated inflammatory endothelial cells to increase drug concentration at the inflammatory site, which sheds light on new strategies for treating neutrophil-mediated inflammatory diseases and practicing the concept of "one drug for multiple diseases".
Animals ; Liposomes ; Rats ; Nanomedicine ; E-Selectin ; Drug Delivery Systems ; Inflammation/drug therapy* ; Mice ; Doxorubicin/analogs & derivatives* ; Zebrafish ; Acute Lung Injury/drug therapy*

Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

Objective:To explore the effect of short-term mindfulness behavior training on body image, negative emotions and mindfulness level of pregnant women with recurrent spontaneous abortion (RSA) .Methods:From October 2020 to October 2021, 50 RSA pregnant women admitted to the Department of Gynecology of Wuxi Woman and Enfants Care Hospital were selected as the study subject using convenience sampling. Pregnant women were divided into an intervention group and a control group using a random number table method, with 25 cases in each group. During the research process, two cases were lost in the intervention group and two cases in the control group, and 46 cases were ultimately completed, with 23 cases in each group. The control group received routine nursing, while the intervention group received a 4-week mindfulness behavior training on this basis. Body Image in Pregnancy Scale (BIPS), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and Mindful Attention Awareness Scale (MAAS) were used to evaluate the effect of intervention.Results:After intervention, the BIPS, SAS, SDS scores of pregnant women in the intervention group were lower than those in the control group, while the MAAS scores were higher than those in the control group, with statistically significant differences ( P<0.05) . Conclusions:Short-term mindfulness behavior training can improve the body image and negative emotions of pregnant women with RSA, and can improve the level of mindfulness attention awareness.

Objective:Explore the establishment of a fast, stable and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for detecting the level of m6A modification in RNA and its application.Methods:The degree of m6A in RNA can be expressed as the ratio of m6A and adenosine (A) in concentration, which can be determined by ESI source positive ion multiple reaction monitoring (MRM) mode. The established method was verified by analyzing three quality control samples (m6A: 4, 40, 400 nmol/L; A: 40, 400, 4 000 nmol/L) with three different concentrations of low, medium, and high. The method was used to detect the degree of m6A in RNA from mouse spleen T cells treated in different ways. The t test was used to compare the differences between the two groups of data. Results:The established method had a good Linearity ( R2>0.99) in a range of 1-500 nmol/L for m6A and 10-5 000 nmol/L for A. The limit of detection (LOD) was 1 nmol/L for m6A and 10 nmol/L for A. The recoveries were between 98.9% and 116.5%. The intra-day ( n=5) RSDs and the inter-day ( n=15, 5 days) RSDs were 2.4%-9.5% and 4.4%-9.6%, respectively. And this method was used to detect the degree of m6A in the RNA from mouse spleen T cells cultured in different conditions. The results showed that the m6A modification level in the RNA of primary CD8 +T cell was 0.271 5±0.017 9, and the m6A modification level in the RNA of primary CD8 +T cell with IL-27 was 0.251 7±0.015 0, indicating that primary CD8 +T cells have a higher level of RNA methylation. Conclusion:This research has established a fast, simplemethylation degree in RNA with HPLC-MS/MS. This method is easy to be popularized and is suitable for the detection of large quantity of samples, and of great significance in analyzing the relationship between methylation and diseases.

Objective:Explore the establishment of a fast, stable and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for detecting the level of m6A modification in RNA and its application.Methods:The degree of m6A in RNA can be expressed as the ratio of m6A and adenosine (A) in concentration, which can be determined by ESI source positive ion multiple reaction monitoring (MRM) mode. The established method was verified by analyzing three quality control samples (m6A: 4, 40, 400 nmol/L; A: 40, 400, 4 000 nmol/L) with three different concentrations of low, medium, and high. The method was used to detect the degree of m6A in RNA from mouse spleen T cells treated in different ways. The t test was used to compare the differences between the two groups of data. Results:The established method had a good Linearity ( R2>0.99) in a range of 1-500 nmol/L for m6A and 10-5 000 nmol/L for A. The limit of detection (LOD) was 1 nmol/L for m6A and 10 nmol/L for A. The recoveries were between 98.9% and 116.5%. The intra-day ( n=5) RSDs and the inter-day ( n=15, 5 days) RSDs were 2.4%-9.5% and 4.4%-9.6%, respectively. And this method was used to detect the degree of m6A in the RNA from mouse spleen T cells cultured in different conditions. The results showed that the m6A modification level in the RNA of primary CD8 +T cell was 0.271 5±0.017 9, and the m6A modification level in the RNA of primary CD8 +T cell with IL-27 was 0.251 7±0.015 0, indicating that primary CD8 +T cells have a higher level of RNA methylation. Conclusion:This research has established a fast, simplemethylation degree in RNA with HPLC-MS/MS. This method is easy to be popularized and is suitable for the detection of large quantity of samples, and of great significance in analyzing the relationship between methylation and diseases.

Objective: To explore the genetic basis for a family with non-syndromic autosomal recessive deafness. Methods: The proband and her parents were subjected to physical and audiological examinations. With genomic DNA extracted from peripheral blood samples, next-generation sequencing was carried out using a panel for deafness genes. Suspected mutation was validated by Sanger sequencing and qPCR analysis of her parents. Results: The proband presented bilateral severe sensorineural hearing loss at three days after birth. Her auditory threshold was 110-120 dBnHL but with absence of vestibular and retinal symptoms. Her brother also had deafness but her parents were normal. No abnormality was found upon physical examination of her family members, while audiological examination showed no middle ear or retrocochlear diseases. Next-generation sequencing identified compound heterozygous mutations of the MYO7A gene, including a previously known c. 462C>A (p. Cys154Ter) and a novel EX43_46 Del, which were respectively derived from her mother and father. Conclusion The compound heterozygous mutations of the MYO7A gene probably underlie the disease in this family. Our findings has enriched the mutation spectrum for non-syndromic autosomal recessive deafness 2.

OBJECTIVE: To explore the genetic basis for a family with non-syndromic autosomal recessive deafness. METHODS: The proband and her parents were subjected to physical and audiological examinations. With genomic DNA extracted from peripheral blood samples, next-generation sequencing was carried out using a panel for deafness genes. Suspected mutation was validated by Sanger sequencing and qPCR analysis of her parents. RESULTS: The proband presented bilateral severe sensorineural hearing loss at three days after birth. Her auditory threshold was 110-120 dBnHL but with absence of vestibular and retinal symptoms. Her brother also had deafness but her parents were normal. No abnormality was found upon physical examination of her family members, while audiological examination showed no middle ear or retrocochlear diseases. Next-generation sequencing identified compound heterozygous mutations of the MYO7A gene, including a previously known c.462C>A (p. Cys154Ter) and a novel EX43_46 Del, which were respectively derived from her mother and father. CONCLUSION The compound heterozygous mutations of the MYO7A gene probably underlie the disease in this family. Our findings has enriched the mutation spectrum for non-syndromic autosomal recessive deafness 2.
Female ; Hearing Loss, Sensorineural ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mutation ; Myosins ; genetics ; Pedigree

Objective: To investigate the expression and clinical significance of long-chain non-coding RNA brain cytoplasmic RNA 1 (BCYRN1) in serum of patients with non-small cell lung cancer. Methods: 74 patients with non-small cell lung cancer (NSCLC) diagnosed and treated in our hospital were selected as the experimental group, and 50 healthy subjects were selected as the control group. The expression of BCYRN1 in serum of NSCLC and control group was detected by real-time quantitative polymerase chain reaction (qRT-PCR). The patients′ clinical pathology data were collected and followed up. To analyze the relationship between the expression of serum BCYRN1 and clinicopathological parameters of NSCLC patients, and the relationship between BCYRN1 expression in the diagnosis and prediction of NSCLC prognosis. Results: The relative expression of BCYRN1 in serum of NSCLC patients was 2.84±0.95, which was significantly higher than that of healthy controls (1.16±0.50) (P<0.05). The level of serum BCYRN1 in patients with NSCLC with tumor size >3 cm was significantly higher than that in patients with tumor size ≤3 cm (P<0.05). The level of BCYRN1 in patients with tumor node metastasis (TNM) Ⅲ+ Ⅳ was significantly higher than that in patients with stage Ⅰ+ Ⅱ (P<0.05). Patients with low differentiation and positive lymph node metastasis had higher serum BCYRN1 than those with moderate to high grade and lymph node metastasis (P<0.05). The receiver operating characteristic (ROC) curve analysis showed that the area under the curve was 0.847 (95% CI: 0.772-0.922, P=0.000), and the sensitivity and specificity were 68.9% and 88.0%, respectively. The median progression free survival (PFS) (15 vs 21 months) and overall survival (OS) (19 vs 28 months) of patients with high and low expression of BCYRN1 were statistically significant (P<0.05). High expression of BCYRN1 was an independent risk factor for overall survival in patients with NSCLC. Conclusions BCYRN1 is highly expressed in the serum of NSCLC patients, and high expression of BCYRN1 is closely related to the poor prognosis of patients with NSCLC. It can be used as a novel biomarker and diagnostic target for NSCLC.

Objective To explore the effect of kangaroo mother care(KMC)on breastfeeding, behavior,body temperature and weight of full-term newborn. Methods A total of 80 full-term newborns from March to December of 2017 were selected by the convenience sampling method, and were randomly divided into control group and intervention group, with 40 cases each group. Routine obstetric nursing was provided for the newborns in the control group. In addition,one hour of KMC was provided for the newborns in the intervention group. The LATCH scores, neonatal behaviors, body temperature and weight were observed on daily basis. Meanwhile, an interview was conducted to investigate mothers′attitudes towards KMC. Results The LATCH scores of the intervention group for the second and third days were respectively (6.52±0.81) and (7.75±1.08), which were higher than that in control group (5.95±0.95), (7.02± 1.07). The differences were statistically significant (t=2.887,3.010,P<0.05). The behavioral status of neonates in the intervention group for 3 days was (3.65±1.12), (3.42±0.87), (3.35±1.07), all of which were lower than that in control group (4.57 ± 0.98), (4.50 ± 1.24), (4.65 ± 1.27), and the differences were statistically significant (t=-4.593,-8.285,-7.029, P<0.01). The interviews showed that 100.0％(40/40) of mothers were satisfied with KMC and were very happy in the process.95.0％(38/40)of mothers believe that KMC can increase mother-child relationships.82.5％(33/40)of mothers believe that KMC can keep children quiet.72.5％(29/40)of mothers feel that KMC can relieve pain in the abdomen or perineum. Conclusions In the hospital, 1h of KMC can make breastfeeding more effective and the newborn condition is more stable, which is worthy of clinical application.

To explore the clinical acupoint selection rule of rheumatoid arthritis(RA) treated with acupuncture by literature analysis. The related articles were retrieved in 6 Chinese and English databases,including CNKI,VIP,,PubMed,Medline and Cochrane. We established a holistic acupoint database and a disease location acupoint database. The results show that there are 120 acupuncture prescriptions and 143 acupoints,with the highest frequency of Zusanli(ST 36). Local acupoints are mainly used for disease locations. The highest acupoin-tcombination frequency of 32 for mandibular joint shows Kunlun(BL 60) and Jiexi(ST 41);22 for finger joint,Baxie(EX-UE 9) and Zusanli(ST 36);28 for wrist joint,Yangxi(LI 5) and Yangchi(TE 4);24 for elbow joint,Quchi(LI 11) and Zusanli(ST 36);21 for shoulder joint,Jianyu(LI 15) and Zusanli(ST 36);13 for spine joint,Yaoyangguan(GV 3) and Shenzhu(GV 12);18 for hip joint,Zhibian(BL 54) and Huantiao(GB 30);20 for knee joint,Shenshu(BL 23) and Yanglingquan(GB 34);32 for ankle joint,Kunlun(BL 60) and Jiexi(ST 41);22 for toe joint,Baxie(EX-UE 9) and Zusanli(ST 36);25 for whole body joints,Yanglingquan(GB 34) and Zusanli(ST 36). Thirty new acupoint prescriptions are found by entropy clustering analysis for different disease regions induced by RA. There exists the acupoint selection rule for acupuncture treating RA and the new prescriptions need to be clinical verification.