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*

Humans ; Female ; Diagnosis, Differential ; Breast/pathology* ; Carcinoma, Intraductal, Noninfiltrating/pathology* ; Breast Neoplasms/pathology*

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

[Abstract] Objective To explore the distribution situation of microRNA(miR) -30 gene single-nucleotide sites rs1192037A / T polymorphisms in Guangxi Zhuang population and compare its distribution differences with other populations and to analyze level of common blood lipid indexes in genotypes. Methods SNPscan was used to detect rs1192037A / T locus genotyping in 236 volunteers of Zhuang nationality in Guangxi. The genotypes and allele frequencies of rs1192037A / T locus genotyping in different genders and groups were analyzed. The levels of common blood lipids in the subjects were detected by roche automatic biochemical apparatus. Results Three genotypes of AA, AT and TT were found in rs1192037 A / T with the frequency distribution of 11. 0%, 38. 6% and 50. 4%, respectively. No significant differences in genotypes and alleles frequencies of rs1192037 A / T between different genders in Guangxi Zhuang population were observed (P > 0. 05) . However,there were significant differences in the genotype and allele frequency of miR-30 gene rs1192037 A / T in Guangxi Zhuang population compared with those of Europeans, Japanese, Africans, Mexicans and Indians published by HapMap (P<0. 05), and there were not significant difference in genotypes and allele frequencies in population of HCB and JTP (P>0. 05) . There were significant differences in the levels of TG among the 3 genotypes of rs1192037 A / T, and the TG levels of AT and TT genotypes were significantly higher than AA genotypes. Conclusion There are different degrees of rs1192037 A / T polymorphisms of miR-30 gene among Guangxi population and other ethnic populations and other regions. The polymorphism of rs1192037 A / T is related to the level of TG.

Objective:To explore the value of endoscopic ultrasonography-guided carbon nanoparticles tattooing for preoperative localization of laparoscopic surgery for rectal cancer.Methods:Sixty patients diagnosed as having rectal cancer who underwent laparoscopic radical resection in the 900th Hospital of Joint Logistics Support Force from April 2018 to April 2019 were randomly divided into the endoscopic ultrasonography-guided tattoo group (group A), the colonoscopy-guided tattoo group (group B) and the control group (group C) by random number table. The leakage rate of dye in intestinal tract, complications, and the tattooed serosa stained with carbon nanoparticles during laparoscopic surgery were recorded. Identification time of lesions, the total operation time, the length of resected rectal segment, tumor distance to distal resection margin, and the rate of anal preservation were analyzed and the postoperative pathology were compared.Results:In group A, endoscopic ultrasonography revealed 2 cases of suspected tumor extension toward the anal side within distal intestinal wall. The extension length was 0.42 cm and 0.71 cm respectively, and the extension length was 0.36 cm and 0.64 cm under microscope respectively. In group B, the pathology result showed that the extension length was 0.53 cm under microscope. In group C, the pathology result showed that the extension length were 0.43 cm, 0.36 cm and 0.28 cm under microscope respectively. Obvious black staining in the rectal serosa was found in all tattooed patients during the surgery. There were scattered black staining spots at the surface of peritoneum and mesentery in 3 cases in group B. The identification time of lesions in group A and B were shorter than that in group C (1.29 ± 0.87 min, 1.31 ± 0.63 min VS 15.3 ± 10.50 min, P<0.05). The total operation time in group A and B were shorter than that in group C (176.12 ± 27.64 min, 175.67 ± 26.48 min VS 198.65 ± 38.67 min, P<0.05). The length of resected rectal segment in group A and B were shorter than that in group C (11.81 ± 5.76 cm, 12.31 ± 3.94 cm VS 15.24 ± 4.12 cm, P<0.05). The tumor distance to distal resection margin in group A and B were shorter than that in group C (3.61 ± 1.26 cm, 4.57 ± 1.58 cm VS 6.13 ± 2.47 cm, P<0.05). Anal preservation rates of three groups were 65.0% (13/20), 60.0% (12/20), 40.0% (8/20) respectively with no significant difference ( P>0.05). No residual tumor cells were found in any specimens. Conclusion:Carbon nanoparticles tattooing guided by endoscopic ultrasonography could reduce unnecessary intestinal segment incision and shorten the operation time. It can also reveal tumor extension toward the anal side within intestinal wall, which provides more accurate localization for the distal incision of the lower rectal cancer.

[Abstract] Objective To explore the association between rs16927589, rs77418916, rs8108402 of the family microRNA(miR)-181 polymorphisms and ischemic stroke(IS),and compare the expression of miR-181 genes between control group and IS group, further explore the association between polymorphisms and the expression levels of genes, to provide assistance for the prevention and treatment of IS. Methods SNaPshot technique and DNA sequencing were used to examine the single nucleotide polymorphism(SNP) genotypes of 349 patients of IS and 372 controls, serum lipid level was detected by biochemical analyzer 7600; The expression level of miR-181 genes in peripheral blood mononuclear cells of control group and IS group were detected by ABI7500 Real-time PCR. Results The genotype and allele of rs8108402 were compared between the control group and IS group, and it was found that compared with CC genotype, the risk of IS was significantly increased among people with CT genotype, TT genotype was opposite [CC vs CT:odds ratio(OR)= 1. 56,95% confidence interval(CI),1. 11-2. 18,P= 0. 011;CC vs TT: OR= 0. 25, 95% CI,0. 10-0. 62, P= 0. 003]. However, there were no correlation with IS of rs16927589 and rs77418916 polymorphisms. Stratified analysis of rs8108402 showed that the low-density lipoprotein (LDL-C) of IS patients with CC genotype was higher than that of IS patients with CT genotype (P< 0. 05), and the polymorphism of rs8108402 might be correlated with the clinical manifestations of IS. In IS group, the expression of miR-181a, miR-181b, miR-181c were obviously higher than that in control group, the difference was statistically significant (P<0. 05), while the expression of miR-181 d significantly lower than the control group, but the difference was not statistically significant (P>0. 05). Further analysis of rs8108402 polymorphism and gene expression level showed no correlation between rs8108402 polymorphism and gene expression level. Conclusion The CT and TT genotypes at rs8108402 of miR-181c increase the risk of IS, while the CTC haplotype increase the risk of IS. The polymorphism of rs8108402 is correlated with the level of LDL-C. There are significant differences in the expression of miR-181 gene clusters between the normal control group and the IS group, and miR-181 clusters may be potential predictive targets and therapeutic targets of IS.

Background The hearing of Chinese young adults is far less sensitive than 0 dB defined by international standards, with the threshold values mostly being at double digits, which is worthy of investigation. Objective To study the influencing factors of hearing threshold measurement. Methods The hearing measurements were conducted in two different ways, one was a standard method performed in a specialized audiometry experiment room, and the other one was an on-site audiometry test which included a daily examination of hearing and an onsite hearing test. From the workers who participated in the occupational health examination, 300 people were randomly selected as experimental subjects, and their hearing was measured in the hearing examination room of the Occupational Disease Prevention and Treatment Institute according to standard methods. A total of 9 766 workers from the General Motors factory were included in the daily group, and their hearing thresholds were measured in the hearing examination room in the factory. There were 4 617 people in the onsite group, and their hearing was measured in the test chamber of our mobile medical vehicle in their factories. The hearing threshold data of the three groups, i.e. experiment, daily examination and on-site, was compared and analyzed. In addition, the environmental noise in the hearing examination room and the mobile test chamber was measured. Results The hearing threshold value of the experimental group was the lowest. Despite this, its dB value remained at double digits at any frequency band. The hearing value of the daily group was in the middle. The onsite group had the highest hearing threshold, which was 58.2% higher than that of the experimental group. As the hearing data was not normally distributed, Kruskal-Wallis non-parametric test was conducted for statistical analysis. It was found that the hearing threshold difference among the three groups was statistically significant at all the frequency band (P< 0.01). The ambient noise level was 23.9-28.3 dB(A) in the hearing examination room, and 32.5 - 67.9 dB (A) in the mobile test chamber. Age and gender were not confounding factors to the results. Conclusion The hearing test method and its environmental noise were able to make the threshold measurements shift up significantly. The environmental noise of the mobile test chamber in the examination vehicle has exceeded the standard and needs to be improved.

To investigate the potential molecular mechanism of the combination of Platycodonis Radix and Lilii Bulbus with the homology of medicine and food in the treatment of pneumonia by means of network pharmacology and in vitro verification experiment. Under the condition of bioavailability(OB)≥30% and drug-like(DL)≥0.18, the active components of Platycodonis Radix and Lilii Bulbus were screened in TCMSP database; the prediction targets of active components were searched from TCMSP, DrugBank and other databases, and the potential targets of pneumonia were obtained through GeneCards and OMIM database. The common targets were obtained by the intersection of drug and disease targets. The PPI network of common targets was constructed by STRING 11.0, and the core targets were obtained by topological analysis. Then the core targets received GO and KEGG analysis with use of WebGestalt and Metascape. The "component-target-pathway" network was constructed with the help of Cytoscape 3.7.1 software, and the component-target molecular docking verification was carried out with Discovery Studio 2016 software. Finally, the core targets and pathways were preliminarily verified in vitro. In this study, 12 active components were screened, 225 drug prediction targets and 420 potential diseases targets were obtained based on data mining method, and 14 core targets were obtained by topological analysis, including TNF, MMP9, AKT1, IL4 and IL2. The enrichment results of GO and KEGG showed that "Platycodonis Radix and Lilii Bulbus" drug pair may regulate inflammation, cell growth and metabolism by acting on 20 key signaling pathways such as TNF and IL-17, thereby exerting anti-pneumonia effects. The results of molecular docking showed that 12 active components had good binding ability with 14 core targets. In vitro experiment results showed that the core components of "Platycodonis Radix and Lilii Bulbus" drug pair could inhibit the expression of MMP9 and TNF-α by regulating TNF signal pathway. This study confirmed the scientificity and reliability of the prediction results of network pharmacology, and preliminarily revealed the potential molecular mechanism of the compatibility of Platycodonis Radix and Lilii Bulbus in the treatment of pneumonia. It provides a novel insight on systematically exploring the mechanism of the compatible use of Platycodonis Radix and Lilii Bulbus, and has a certain reference value for the research, development and application of new drugs.
Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Pneumonia/drug therapy* ; Reproducibility of Results

Objective To study the distribution of hypoxia inducible factor ( HIF ) 3A gene single nucleotide polymorphisms ( SNPs ) in Guangxi Han population and compare their distribution differences with different populations. Methods We conducted SNPscan technique to detect the genotypes of rsl 1672731 and rs2072491 on 286 Guangxi Han population included in the study and statistically analyzed the genotype and allele frequency and the HapMap-CEU, HapMap- HCB, HapMap-JPT, HapMap-GIH and HapMap-MEX data differences. Results Three genotypes, AA, AG and GG, were found in rsl 1672731 of HIF3A, with frequency of 42.7%, 45. 5% and 11. 8%, respectively, the allele frequencies of A and G were 65.5% and 34.5%, respectively. Three genotypes of CC, CT and TT, were found for rs2072491 with frequency distributions of 47.6%, 43.0% and 9.4%, respectively, the allele frequencies of C and T were 69.1% and 30.9%, respectively. There was no significant differences in genotype and allele frequencies of rsl 1672731 and rs2072491 between different genders in Guangxi Han population (P>0. 05). However, compared with the typing data of CEU, HCB, JPT, GHI, TSI and MEX from human genome project (HapMap), the genotype and allele frequencies of rsl 1672731 and rs2072491 were not significantly different from those of HCB and JPT (P>0. 05). The genotype and allele frequencies of rsl 1672731 and rs2072491 were statistically different with the date of CEU, GIH, TSI and MEX published by the HapMap (P<0.05). Conclusion The polymorphisms of HIF3A gene rsl 1672731 and rs2072491 have differences on different populations.

OBJECTIVE: To investigate the prevalence and influencing factors of low back pain in workers in automobile manufacturing plants. METHODS: A judgment sampling method was used to select 394 workers with working length ≥1 year in an automobile manufacturing plant as study subjects. A questionnaire survey was conducted to investigate the prevalence of low back pain in these workers using the Nordic Musculoskeletal Disorders Questionnaire. RESULTS: The prevalence of low back pain in these study subjects was 28. 9%( 114/394). The multivariate logistic regression analysis results showed that the relative risk ranked from high to low is as follow: uncomfortable working posture [Odds ratio( OR) =7. 31,95% confidence interval( 95% CI) = 2. 92-18. 28],feeling tired after work( OR = 5. 34,95% CI = 1. 22-23. 32],the commu time more than 30 minutes( OR = 2. 76,95% CI = 1. 38-5. 52),insufficient operating space( OR = 2. 22,95% CI = 1. 28-3. 83),hand or arm frequently used at work( OR = 2. 08,95% CI = 1. 14-3. 78) and age( OR = 2. 00,95% CI = 1. 19-3. 35),that were all risk factors of low back pain( P < 0. 05). CONCLUSION: The frequent use of hand or arm at work,insufficient operating space,uncomfortable working posture,feeling tired after work,and long commute time are the main influencing factors affecting the low back pain of automobile manufacturing workers.