Poloxamer， as a non-ionic surfactant， exhibits a unique triblock [polyethylene oxide-poly （propylene oxide）-polyethylene oxide] structure， which endows it with broad application potential in various fields， including solid dispersion technology， nanotechnology， gel technology， biologics， gene engineering and 3D printing. As a carrier， it enhances the solubility and bioavailability of poorly soluble drugs. In the field of nanotechnology， it serves as a stabilizer etc.， enriching preparation methods. In gel technology， its self-assembly behavior and thermosensitive properties facilitate controlled drug release. In biologics， it improves targeting efficiency and reduces side effects. In gene engineering， it enhances delivery efficiency and expression levels. In 3D printing， it provides novel strategies for precise drug release control and the production of high-quality biological products. As a versatile material， poloxamer holds promising prospects in the pharmaceutical field.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

[摘 要] 目的：探讨2',4'-二羟基查尔酮（D2）通过调控miR-7-5p诱导自噬，抑制结直肠癌细胞增殖、迁移及上皮间质转化（EMT）的分子机制。方法：选取结直肠癌细胞系HCT-15、SW620为研究对象，分别用不同浓度（0、12.5、25、50 µmol/L）的D2处理细胞，采用MTT法和平板克隆实验检测细胞增殖活力及克隆形成能力，划痕愈合实验及Transwell实验评估细胞迁移能力，WB法检测EMT相关蛋白、自噬相关蛋白及PI3K/AKT/mTOR信号通路蛋白的表达情况，免疫荧光染色法观察自噬小体的形成。基于TCGA数据库分析miR-7-5p在结直肠癌中的表达水平，并借助KEGG富集分析探究miR-7-5p与结直肠癌的关联。运用RT-qPCR检测miR-7-5p的表达量，同时采用慢病毒转染技术构建miR-7-5p稳定敲低或过表达的细胞系。结果：D2抑制结直肠癌细胞的增殖、迁移及EMT进程（P < 0.05或P < 0.01）。TCGA数据库分析及KEGG富集分析显示，miR-7-5p在结直肠癌中呈低表达，且与结直肠癌的发生有密切关联。12.5、25、50 µmol/L D2处理均可上调HCT-15、SW620细胞miR-7-5p的表达水平（均P < 0.01）。25 µmol/L D2处理组HCT-15、SW620细胞中 LC3、p-ULK1等自噬相关蛋白表达增加，而PI3K/AKT/mTOR信号通路受到抑制（均P < 0.05），细胞内自噬小体数量增加（均P < 0.01）；与D2单独处理组相比，经 D2处理的miR-7-5p敲减细胞中LC3、p-ULK表达量有所下降（P < 0.05或P < 0.01）。结论：D2通过调控miR-7-5p诱导自噬，抑制结直肠癌细胞的增殖、迁移及EMT进程，其机制可能与抑制PI3K/AKT/mTOR信号通路有关。

ObjectiveTo investigate the expression of C1q tumor necrosis factor-related protein 3 （C1QTNF3） in liver cancer tissue， its association with the clinicopathological features of patients， and its potential value in predicting the prognosis of liver cancer. MethodsRelated data were collected from TIMER， UALCAN， TNMplot， and GEO databases， and the bioinformatics methods were used to measure the expression level of C1QTNF3 in pan-cancer， normal tissue/liver cancer tissue， and cancerous tissue/paracancerous tissue. Cancerous and paracancerous tissue samples were collected from 90 patients with liver cancer， and related clinical data were collected， including age， sex， tumor diameter， and tumor number. The independent-samples t test or the paired t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used to investigate the association between the expression level of C1QTNF3 and the survival of patients with liver cancer. The Cox regression model was used to identify the risk factors for the prognosis of patients with liver cancer， and the receiver operating characteristic （ROC） curve was used to analyze the ability of C1QTNF3 expression at different time points for predicting the prognosis of patients with liver cancer. ResultsThe bioinformatics analysis showed that the expression of C1QTNF3 was upregulated in various malignant tumors， especially in liver cancer tissue （P<0.001）， and the expression level of C1QTNF3 in liver cancer tissue was significantly higher than that in normal tissue and paracancerous tissues （all P<0.01）. The immunohistochemical staining results of 90 patients with liver cancer showed that C1QTNF3 was mainly expressed in cytoplasm， with a small amount in nucleus， and it had negative expression in paracancerous tissue and positive expression in liver cancer tissue. The positive expression rate and strong positive expression rate of C1QTNF3 protein in liver cancer tissue were significantly higher than those in paracancerous tissue （positive expression rate： 76.67% vs 33.33%， χ²=34.141， P<0.01； strong positive expression rate： 54.44% vs 5.56%， χ²=51.217， P<0.01）. The liver cancer patients with a tumor diameter of ≥5 cm， an advanced stage， the presence of liver cirrhosis， negative HBsAg， and gamma-glutamyl transpeptidase （GGT）≥50 U/L had a significantly higher strong positive expression rate of C1QTNF3 protein than those with a tumor diameter of <5 cm， an early stage， the absence of liver cirrhosis， positive HBsAg， and GGT<50 U/L （all P<0.05）. The univariate Cox regression analysis showed that tumor diameter， recurrence， and C1QTNF3 expression were influencing factors for the prognosis of patients with liver cancer （all P<0.05）， and the multivariate Cox regression analysis showed that the expression level of C1QTNF3 and recurrence were independent risk factors for the survival of patients with liver cancer （both P<0.05）. The survival curve analysis showed that for all patients with liver cancer， the patients with high （strong positive） expression of C1QTNF3 had significantly lower overall survival rate and disease-free survival rate than those with low expression （χ²=17.010 and 13.647， both P<0.001）； for liver cancer patients with a tumor diameter of ≥5 cm， an early/advanced stage， recurrence， the presence of liver cirrhosis， positive HBsAg， alanine aminotransferase （ALT） <40 U/L， ALT≥40 U/L， and GGT≥50 U/L， the patients with high expression of C1QTNF3 had a significant reduction in overall survival rate （χ²=11.086， 5.578， 5.295， 19.159， 16.391， 13.774， 10.119， 8.152， and 12.035， all P<0.05）. The ROC curve analysis showed that C1QTNF3 expression had the strongest predictive potential at 5 years， with an area under the ROC curve of 0.77. ConclusionC1QTNF3 is highly expressed in liver cancer tissue， and the expression level of C1QTNF3 and recurrence are closely associated with the survival of patients with liver cancer. Patients with high expression of C1QTNF3 protein tend to have a lower survival rate.

OBJECTIVE: To observe the efficacy of "Biaoben acupoint compatibility" moxibustion for abdominal obesity and its effect on blood lipid, lipid accumulation product (LAP) and cardiometabolic index (CMI). METHODS: A total of 150 patients with abdominal obesity were randomly divided into an observation group (75 cases, 5 cases dropped out) and a control group (75 cases, 6 cases dropped out). The control group received lifestyle guidance. The observation group received "Biaoben acupoint compatibility" moxibustion at Zhongwan (CV12), Guanyuan (CV4) and bilateral Tianshu (ST25), Zusanli (ST36) on the basis of the control group, 20 min each time, once every other day, 3 times a week for 8 weeks. Before and after treatment, the waist circumference, hip circumference, weight, body mass index (BMI) were observed, the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured, and the LAP and CMI were calculated in the two groups. RESULTS: After treatment, the waist circumference, weight and BMI were decreased compared with those before treatment in both groups (P<0.05), the changes of the above indexes in the observation group were larger than those in the control group (P<0.05). After treatment, the hip circumference, TC level, TG level, LAP and CMI in the observation group were decreased compared with those before treatment (P<0.05), the HDL-C level was increased compared with that before treatment (P<0.05)；the changes of the TC level, TG level, LAP, CMI and HDL-C level in the observation group were larger than those in the control group (P<0.05). CONCLUSION "Biaoben acupoint compatibility" moxibustion can reduce the degree of obesity in patients with abdominal obesity, and improve blood lipid and reduce lipid accumulation.
Humans ; Acupuncture Points ; Moxibustion ; Male ; Female ; Middle Aged ; Obesity, Abdominal/blood* ; Adult ; Lipids/blood* ; Lipid Metabolism ; Triglycerides/blood* ; Young Adult ; Treatment Outcome ; Aged

OBJECTIVE: To observe the efficacy and safety of moxibustion in treating patients with central obesity of phlegm-dampness constitution. METHODS: A total of 66 patients with central obesity of phlegm-dampness constitution were randomly assigned to a moxibustion group (n=33, 3 cases dropped out) and a sham moxibustion group (n=33, 4 cases dropped out). The moxibustion group received mild moxibustion combined with lifestyle intervention; the moxibustion was applied at Shenque (CV8) and bilateral Zusanli (ST36), 30 min per session, maintaining a local skin temperature of (43±1) ℃. The sham moxibustion group received simulated moxibustion combined with lifestyle intervention; the simulated moxibustion was applied at the same acupoints, with the same session length, but with a maintained skin temperature of (37±1) ℃. Both groups were treated once every other day, three times per week for 8 consecutive weeks. Obesity-related physical indicators (waist circumference, hip circumference, body weight, body fat percentage, body mass index [BMI]), constitution evaluation indicators (phlegm-dampness constitution conversion score, symptom score), the impact of weight on quality of life-lite (IWQOL-Lite), the hospital anxiety and depression scale (HADS), and the incidence of adverse events were measured before and after treatment, and after 4 weeks of follow-up. RESULTS: Compared with before treatment, both groups showed significant reductions in waist circumference, hip circumference, body weight, body fat percentage, BMI, phlegm-dampness constitution conversion score and symptom score, IWQOL-Lite, and both anxiety and depression subscale scores of HADS after treatment and at follow-up (P<0.001). These improvements were significantly greater in the moxibustion group than those in the sham moxibustion group (P<0.001, P<0.01, P<0.05). One patient in the moxibustion group experienced a mild burn that resolved with routine care; the incidence of adverse reactions was 3.0% (1/33) in the moxibustion group and 0% (0/33) in the sham moxibustion group, with no statistically significant difference (P>0.05). CONCLUSION On the basis of lifestyle intervention, moxibustion effectively improves obesity-related physical indicators, enhances quality of life, alleviates anxiety and depression, and improves the phlegm-dampness constitution in patients with central obesity. These benefits persist for at least 4 weeks after treatment.
Humans ; Moxibustion ; Male ; Female ; Middle Aged ; Adult ; Obesity, Abdominal/psychology* ; Acupuncture Points ; Treatment Outcome ; Aged ; Quality of Life ; Young Adult ; Body Mass Index

Objective To investigate whether miR-15b-5p can alleviate airway inflammation in asthma by negatively regulating ubiquitin specific peptidase 9X (USP9X) to down-regulate the expression of phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit α/AKT serine/threonine kinase 1 (PIK3CA/AKT1) pathway. Methods USP9X was predicted to be a direct target of miR-15b-5p by using an online database (miRWalk), and the luciferase reporter gene assay was performed to verify it. Co-immunoprecipitation (CO-IP) was used to verify the direct binding between USP9X and PIK3CA and the role of USP9X and its small molecule inhibitor WP1130 in the deubiquitination of PIK3CA. C57 mice were randomly divided into Control group, OVA group, OVA combined with NC group and miR-15b-5p agomir group, with 10 mice in each group. BEAS-2B cells were induced with interleukin 13 (IL-13) and treated with miR-15b-5p mimic. HE, Masson, PAS, immunohistochemistry, immunofluorescence staining, flow cytometry, Western blot and quantitative real-time PCR(qRT-PCR) were performed. Results It was found that the administration of miR-15b-5p agomir and mimic could reduce peribronchial inflammatory cells and improve airway inflammation, and miR-15b-5p could target negative regulation of USP9X. USP9X could directly bind to PIK3CA and regulate PIK3CA level in a proteasome-dependent manner, and USP9X could deubiquitinate K29-linked PIK3CA protein. Down-regulation of USP9X could increase PIK3CA ubiquitination level. WP1130, a small molecule inhibitor of USP9X, has the same effect as knockdown of USP9X, both of which could increase the ubiquitination level of PIK3CA and reduce the protein level of PIK3CA. Conclusion The miR-15b-5p/USP9X/PIK3CA/AKT1 signaling pathway may provide potential therapeutic targets for asthma.
Animals ; MicroRNAs/metabolism* ; Asthma/pathology* ; Class I Phosphatidylinositol 3-Kinases/genetics* ; Ubiquitin Thiolesterase/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Humans ; Inflammation/genetics* ; Cell Line ; Female ; Male

Objective:To investigate the application value of nasolabial flaps in addressing tissue defects after resection of benign and malignant nasal vestibular lesions. Methods:The clinical data of patients with benign and malignant nasal vestibular lesions were analyzed retrospectively. There were 4 cases of squamous cell carcinoma, 2 cases of black hairy nevus and 1 case of chronic proliferative inflammatory lesions, all of which were repaired by adjacent nasolabial flap. Results:After 6 months of follow-up, none of the patients developed nasal vestibular contracture or nostril stenosis, and postoperative nasal ventilation function was good. Conclusion:The preoperative design of individual nasolabial flaps is very important for maintaining maxillofacial aesthetics, protectingthe nasolabial framework, and preserving postoperative nasal ventilation function.
Humans ; Retrospective Studies ; Middle Aged ; Nose Neoplasms/surgery* ; Surgical Flaps ; Male ; Female ; Adult ; Nose/surgery* ; Plastic Surgery Procedures/methods* ; Carcinoma, Squamous Cell/surgery* ; Aged ; Skin Transplantation

OBJECTIVE: To analyze the risk factors of hypophosphatemia in patients with acute respiratory distress syndrome (ARDS). METHODS: A retrospective case-control study was conducted. The clinical data of the patients with ARDS admitted to Yanbian University Affiliated Hospital from January 2018 to October 2022 were collected. According to the 1-day serum phosphorus level after intensive care unit (ICU) admission, the patients with normal (0.80-1.45 mmol/L) or elevated (> 1.45 mmol/L) serum phosphorus levels were included in the non-hypophosphatemia group, while those with phosphorus levels lower than 0.80 mmol/L were included in the hypophosphatemia group. The differences in the inflammatory indicators [neutrophils percentage (NEU%), neutrophil count (NEU), lymphocyte count (LYM), high-sensitivity C-reactive protein (hs-CRP)], proteins [total protein (TP), albumin (Alb), prealbumin (PA)], blood lactic acid (Lac), neutrophil/lymphocyte ratio (NLR), neutrophil/albumin ratio (NAR), and blood lactic acid/albumin ratio (L/A) at 1, 2, 4, 6 and 8 days after ICU admission were compared between the two groups. The partial correlation method was used to analyze the correlation between the 1-day serum phosphorus level after ICU admission and the above indicators. Multivariate Logistic regression analysis was adopted to explore the risk factors of hypophosphatemia in patients with ARDS. RESULTS: All 110 patients were enrolled in the final analysis, among which there were 56 cases in the hypophosphatemia group and 54 cases in the non-hypophosphatemia group. At 1 day and 2 days after ICU admission, NEU% in the hypophosphatemia group were significantly higher than those in the non-hypophosphatemia group (1 day: 0.87±0.08 vs. 0.82±0.12, 2 days: 0.87±0.05 vs. 0.83±0.11, both P < 0.05). As the ICU admission time prolonged, LYM in the hypophosphatemia group was basically on the rise, and NEU%, hs-CRP, and NLR were first decreased and then increased. At 1 day after ICU admission, TP, Alb and PA in the hypophosphatemia group were significantly lower than those in the non-hypophosphatemia group [TP (g/L): 52.96±8.42 vs. 56.47±8.36, Alb (g/L): 29.73±5.83 vs. 33.08±7.35, PA (g/L): 69.95±50.72 vs. 121.50±82.42, all P < 0.05]. As the ICU admission time prolonged, TP and Alb in the hypophosphatemia group were basically showed a trend of first decreasing and then increasing, but at 8 days, Alb was still lower than that at 1 day, and PA basically showed an upward trend. In the non-hypophosphatemia group, the change trends of TP and Alb were consistent with those in the hypophosphatemia group. Lac and L/A both showed a downward trend in the two groups. Partial correlation analysis showed that 1-day serum phosphorus level after ICU admission was significantly negatively correlated with NEU% and hs-CRP (r value was -0.229 and -0.286, respectively, both P < 0.05), and significantly positively correlated with LYM and PA (r value was 0.231 and 0.311, respectively, both P < 0.05). Multivariate Logistic regression analysis showed that 1-day NEU% [odds ratio (OR) = 0.932, 95% confidence interval (95%CI) was 0.873-0.996, P = 0.038] and Alb (OR = 1.167, 95%CI was 1.040-1.308, P = 0.008) were the independent risk factors for hypophosphatemia in ARDS patients. CONCLUSION NEU% and Alb at 1 day after ICU admission are independent risk factors for hypophosphatemia in patients with ARDS.
Humans ; Hypophosphatemia/etiology* ; Respiratory Distress Syndrome/blood* ; Risk Factors ; Retrospective Studies ; Case-Control Studies ; Intensive Care Units ; Male ; Female ; Phosphorus/blood* ; Middle Aged ; Neutrophils ; Aged ; C-Reactive Protein

Objective:To investigate the prognostic value of N-terminal B-type brain natriuretic peptide precursor (NT-proBNP), cardiac troponin I (cTnI) and aVL lead T-wave changes in acute coronary syndrome (ACS).Methods:Clinical data of 162 patients with ACS admitted to the Emergency Chest Pain Center of the Affiliated Hospital of Jining Medical University from January 2020 to December 2021 were retrospectively collected, including 84 patients with unstable angina pectoris (UAP) and 46 patients with ST-segment elevation myocardial infarction (STEMI). 32 patients with non-ST elevation myocardial infarction (NSTEMI); There were 66 patients with single-vessel disease, 70 patients with double-vessel disease, 26 patients with multi-vessel disease, and 51 patients with major cardiovascular adverse events (MACE). The levels of NT-proBNP, cTnI and T-wave change ratio of aVL lead were compared in different patients.Results:The NT-proBNP and cTnI of UAP patients were 510.42(365.56, 630.54)pg/ml and 8.20(6.50, 10.50)ng/ml, respectively, which were significantly lower than those of STEMI and NSTEMI patients (all P<0.05). There was no significant difference in NT-proBNP and cTnI between STEMI and NSTEMI patients (all P>0.05). The T-wave change proportions of NT-proBNP, cTnI and aVL leads in patients with multi-vessel lesions were 804.90(680.87, 980.05)pg/ml, 13.90(10.12, 15.65)ng/ml and 88.46%(23/26), respectively. It was significantly higher than that in patients with single and double vessel lesions (all P<0.05). The T-wave change ratio of NT-proBNP, cTnI and aVL leads in patients with double-vessel disease was 680.84(525.50, 810.62)pg/ml, 10.40(8.92, 13.60)ng/ml and 67.14%(47/70), respectively, which was significantly higher than that in patients with single-vessel disease (all P<0.05). The proportions of T-wave changes of NT-proBNP, cTnI and aVL leads in MACE patients were 744.54(621.17, 905.54)pg/ml, 12.21(8.65, 15.54)ng/ml and 86.27%(44/51), respectively. It was significantly higher than those without MACE (all P<0.05). The area under receiver operating characteristic (ROC) curve of NT-proBNP, cTnI and aVL lead T-wave changes independently and jointly predicted the occurrence of MACE were 0.937, 0.677, 0.706 and 0.799, respectively, among which NT-proBNP had a higher value in predicting the occurrence of MACE. Conclusions:The T-wave changes of NT-proBNP, cTnI and aVL leads are related to the type of lesions, the number of lesions and the occurrence of MACE in ACS patients, and NT-proBNP has a high value in predicting prognosis.