In the past few decades, microbubbles were widely used as ultrasound contrast agents in the field of tumor imaging. With the development of research, ultrasound targeted microbubble destruction technology combined with drug-loaded microbubbles can achieve precise drug release and play a therapeutic role. As a micron-scale carrier, microbubbles are difficult to penetrate the endothelial cell space of tumors, and nano-scale drug delivery system—nanobubbles came into being. The structure of the two is similar, but the difference in size highlights the unique advantages of nanobubbles in drug delivery. Based on the classification principle of shell materials, this review summarized micro/nanobubbles used for ultrasound diagnosis or treatment and discussed the possible development directions, providing references for the subsequent development.

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.
Mice ; Animals ; Alocasia/metabolism* ; MAP Kinase Signaling System ; Caspase 3/metabolism* ; Apoptosis ; RNA, Messenger/metabolism*

Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C

Objective To explore the inter-rater and within-rater reliability of the 30 categories of the International Classification of Functioning Disability,and Health(ICF)dysfunction set(ICF generic-30 set)in clinical function assessment,to provide a basis for its clinical application.Methods Ninety patients from the Neurorehabilitation Department of the First People's Hospital of Suqian City were enrolled in this study.All patients were evaluated by the same functional evaluator's ICF dysfunction combination at the two time points of admission and discharge for the internal reliability analysis of the evaluator.Thirty patients in the neurorehabilitation department were randomly selected to be evaluated by two ICF function evaluators at the same time to conduct test-retest reliability analysis among evaluators.The internal consistency of the Cronbach's α coefficient test scale,and the intra-group correlation coefficient(ICC)test inter-rater reliability and within-rater reliability.Results The Cronbach's α coefficients of the combination of ICF dysfunction,physical function and activity,and participation in the two subscales were 0.941,0.717,and 0.942,respectively.The inter-rater reliability analysis showed that the ICC of the total score of the scale and the total scores of physical function and activity and participation in the two subscales were 0.998,0.971,0.999(P<0.01),and the inter-rater reliability good;the internal reliability analysis of the evaluator showed that the total score of the scale and the total scores of physical function and activity and participation in the two subscales were 0.988,0.917,0.991(P<0.01),except that b640 sexual function is not applicable,and b130 energy Harmony drive function ICC is 0.558,b280 pain ICC is 0.409,ICC of other combination items is 0.838-0.986(P<0.01),the evaluator's internal reliability is good;90 patients'ICF dysfunction combination scale has 30 categories.The comparison between admission and discharge was statistically significant except that b640 was not applicable for sexual function(P<0.05).Conclusion The combination of ICF dysfunction has good internal consistency and inter-evaluator and intra-evaluator reliability in the functional evaluation of patients in neurorehabilitation department.

Objective:To investigate the value of ultrasonic measurement of the ratio of optic nerve sheath diameter (ONSD) to eyeball transverse diameter(ETD) in the diagnosis and prognosis of intracranial hypertension in patients with craniocerebral trauma.Methods:A total of 120 patients with craniocerebral trauma treated in the Xingtai General Hospital of North China Medical and Health Group from December 2021 to January 2023 were perspectively selected, and they were divided into normal intracranial pressure group (73 cases) and intracranial hypertension group (47 cases) according to the results of intracranial pressure measurements, and the intracranial hypertension group was divided into good prognosis group (20 cases) and poor prognosis group (27 cases) according to the follow-up prognosis. The efficacy of ONSD, ETD and ONSD/ETD in intracranial hypertension diagnosis and prognosis assessment were analyzed by receiver operating characteristic (ROC) curve. Kaplan-Meier method was used to evaluate the 6-month risk of adverse prognosis of patients, and the comparison was made by Log-rank test.Results:The levels of intracranial pressure, ONSD, ONSD/ETD in the normal intracranial pressure group were lower than those in the intracranial hypertension group: (130.73 ± 23.63) mmH 2O (1 mmH 2O = 0.009 8 kPa) vs. (270.11 ± 35.78) mmH 2O, (5.47 ± 0.29) mm vs. (5.78 ± 0.44) mm, 0.246 ± 0.018 vs. 0.263 ± 0.018, there were statistical differences ( P<0.05). The scores of Glasgow Coma Scale (GCS), intracranial pressure, ONSD, ONSD/ETD in the good prognosis group were lower than those in the poor prognosis group: (5.50 ± 1.24) scores vs. (6.41 ± 1.34) scores, (256.15 ± 30.23) mmH 2O vs. (280.44 ± 36.56) mmH 2O, (5.62 ± 0.40) mm vs. (5.90 ± 0.44) mm, 0.254 ± 0.014 vs. 0.270 ± 0.017, there were statistical differences ( P<0.05). ROC curve analysis results showed that the area under the curve (AUC) of ONSD and ONSD/ETD for diagnosing intracranial hypertension in patients with craniocerebral trauma were 0.718 and 0.765, respectively, and the critical values were 5.87 mm and 0.263, respectively. The AUC of ONSD and ONSD/ETD predicting prognosis of intracranial hypertension patients was 0.677 and 0.763, respectively, and the critical values were 5.90 mm and 0.267, respectively. Grouped by the threshold of ONSD/ETD for the prognosis of intracranial hypertension (0.267), the incidence of adverse prognosis in ONSD/ETD > 0.267 group was higher than that in the ONSD/ETD≤0.267 group, there was statistical difference ( P<0.05). Conclusions:ONSD/ETD can be used as an index for diagnosis and prognosis of intracranial hypertension.

Objective To observe whether SaCoVLM laryngeal mask can cause gastroesophageal reflux when the body position changes(lithotomy position and supine position).Methods A total of 70 patients were selected for elective surgery in Shanghai General Hospital from Dec 1st,2021 to Sep 30th,2022.There were 35 patients with ureteroscopy in urology and 35 patients with ankle surgery in trauma orthopedics selected as lithotomy position group and supine position group,respectively.Under SaCoVLM laryngeal mask anesthesia,a dual probe pH electrode was placed in the esophagus to continuously monitor the pH value in the esophagus.The pH values and their changing trends in the lithotomy position and supine position of the esophagus were compared under general anesthesia with SaCoVLM laryngeal mask ventilation,and the possibility of gastroesophageal reflux occurring in both positions was explored.Results The peak airway pressure at each time point(5 min,10 min,15 min,20 min and 30 min)after body position was determined in the two groups,and it in lithotomy position group was significantly higher than that in supine position group,and the difference was statistically significant(P＜0.05).The middle and upper esophageal pH values of the two groups were compared 10 min after laryngeal mask insertion,and it in lithotomy position group(6.045±0.490)was significantly lower than the supine group(6.532±0.366),and the difference was statistically significant(P＜0.05).The middle and upper esophageal pH values of the two groups were compared 10 min and 15 min after laryngeal mask insertion.They in lithotomy position group were significantly lower than those in supine position group,and the differences were statistically significant(10 min:6.045±0.490 vs.6.532±0.366,P=0.031;15 min:5.828±0.487 vs.6.474±0.411,P=0.048).There was no significant difference in the pH of the middle and upper esophagus between the two groups at 1,5,20 and 30 minutes of laryngeal mask insertion.There was no significant difference in the pH value of the esophageal opening between the two groups at each time point after laryngeal mask insertion.Conclusion Under SaCoVLM laryngeal mask ventilation,the risk of gastroesophageal reflux during lithotomy surgery may be higher than during supine surgery.

Objective To characterize the temporal dynamics of endophytic community and key metabolites during the growth developmental stages of Artemisia indica and to explore the effects of endophytes on the medicinal material quality of A.indica from the perspective of microorganism combined with the correlation analysis.Methods In this study,high-throughput sequencing was performed to obtain the temporal dynamics of diversity and composition of endophytic community during the growth stages of A.indica.Key metabolites quantitative analysis were performed using high-performance liquid chromatography and ultraviolet spectrophotometry.Spearman's correlation analysis was further conducted to identify the endophytic communities that were significantly correlated with metabolites.Results There were significant differences in the diversity and composition of endophytic communities during the growth stages of A.indica.Linear discriminant analysis efect size(LEfSe)analyses identified some potential microbial biomarkers,such as Firmicutes,Massilia,Pantoea,Alternaria,Didymella,and Trichomerium.The abundances of some genera were significantly and positively correlated with the content of total polyphenols and total flavonoids(P<0.05),such as Curtobacterium,Pantoea,Tilletiopsis,and Dissoconium.The abundances of Pseudozyma,Ralstonia,and Pleospora were significantly and positively correlated with Chlorogenic acid,Isochlorogenic acid B,Isochlorogenic acid A,and Isochlorogenic acid C(P<0.05).Conclusion This work described the distribution of endophytes and key metabolites during the development stages of A.indica.Some endophytic communities with significant correlation of key metabolites were identified,which provided valuable information to guide the isolation of endophytic strains related to key metabolites and improve the quality of A.indica.

Tetramethylpyrazine is the main component of Ligusticum chuanxiong. Studies have found that tetramethylpyrazine has a good protective effect against cardiovascular diseases. In the heart, tetramethylpyrazine can reduce myocardial ischemia/reperfusion injury by inhibiting oxidative stress, regulating autophagy, and inhibiting cardiomyocyte apoptosis. Tetramethylpyrazine can also reduce the damage of cardiomyocytes caused by inflammation, relieve the fibrosis and hypertrophy of cardiomyocytes in infarcted myocardium, and inhibit the expansion of the cardiac cavity after myocardial infarction. In addition, tetramethylpyrazine also has a protective effect on the improvement of familial dilated cardiomyopathy. Besides, the mechanisms of tetramethylpyrazine on blood vessels are more abundant. It can inhibit endothelial cell apoptosis by reducing oxidative stress, maintain vascular endothelial function and homeostasis by inhibiting inflammation and glycocalyx degradation, and protect vascular endothelial cells by reducing iron overload. Tetramethylpyrazine also has a certain inhibitory effect on thrombosis. It can play an anti-thrombotic effect by reducing inflammatory factors and adhesion molecules, inhibiting platelet aggregation, and suppressing the expression of fibrinogen and von Willebrand factor. In addition, tetramethylpyrazine can also reduce the level of blood lipid in apolipoprotein E-deficient mice, inhibit the subcutaneous deposition of lipids, inhibit the transformation of macrophages into foam cells, and inhibit the proliferation and migration of vascular smooth muscle cells, thereby reducing the formation of atherosclerotic plaque. In combination with network pharmacology, the protective mechanism of tetramethylpyrazine on the cardiovascular system may be mainly achieved through the regulation of phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt), hypoxia-inducible factor 1(HIF-1), and mitogen-activated protein kinase(MAPK) pathways. Tetramethylpyrazine hydrochloride and sodium chloride injection has been approved for clinical application, but some adverse reactions have been found in clinical application, which need to be paid attention to.
Mice ; Animals ; Endothelial Cells/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Myocardial Infarction ; Myocardium/metabolism* ; Myocytes, Cardiac ; Thrombosis ; Inflammation ; Apoptosis

Aim To analyze the effects of berberine on the apoptosis of colon epithelial cells and polymorpho-nuclear neutrophils ( PMNs) in mice with ulcerative colitis ( UC ) by regulating JAK/STAT signaling pathway. Methods The UC mouse models were established by dextran sulfate sodium ( DSS) method and were randomly divided into control group, UC group, low-dose, middle-dose and high-dose berberine groups and positive drug group ( mesalazine enteric-coated tablet group) . In addition, the mice were randomly di¬vided into UC group, high-dose berberine group, AG490 group, and high-dose berberine + AG490 group. Levels of serum tumor necrosis factor a (TNF-α) and interleukin 6 (IL-6) and colon epithelial cell apoptosis and PMN apoptosis were compared among the groups. Western blot was used to detect the expres¬sions of colon tissue apoptosis-related and JAK/STAT signaling pathway-related proteins. Results The lev¬els of serum TNF-α and IL-6, apoptosis rate of colon epithelial cell and protein expressions of Fas, FasL, Bax, caspase-3, p-JAK2/JAK2 and p-STAT3/STAT3 in each dose berberine group and positive drug group were significantly lower than those in UC group (P < 0.05), and the above indicators in berberine groups were reduced gradually (P <0.05) . The PMN apoptosis rate and Bcl-2 protein expression were significantly higher in each dose berberine group and positive drug group than those in UC group (P <0. 05) , and the two indicators increased gradually in berberine groups ( P < 0.05). AG490 could reverse the above effects of berberine ( P < 0. 05 ). Conclusions Berberine can inhibit the apoptosis of colon epithelial cell and promote the apoptosis of PMN in UC mice by regulating the JAK/STAT signaling pathway, and then play a role in the treatment of UC.

Objective:To explore the clinical value of super micro vascular imaging (SMI) in evaluating the microvascular perfusion of diabetes foot treated by tibial transverse bone transport.Methods:A retrospective study of 18 diabetic foot patients who underwent tibial transverse bone transport in the Second Hospital of Shanxi Medical University from May 2019 to December 2021 were analysed, including 12 males and 6 females, with an average age of 64.89±14.34 years (range, 30-90 years). All patients had varying degrees of foot ulcer. Before and after the operation, the blood vessels of the patient's lower leg and foot were examined. The display rate of low-velocity blood flow was compared between color Doppler flow imaging (CDFI) and SMI; the blood flow and vascular index at the beginning of the first dorsal metatarsal artery before and after operation under SMI were compared; the number and length of new blood vessels were also compared before and after operation.Results:All patients were followed up for at least 2 months. CDFI blood flow display rate was 73.6% (106/144), and SMI blood flow display rate was 80.6% (116/144), the difference was statistically significant (χ 2=4.68, P=0.031). Under SMI, the blood flow at the beginning of the first dorsal metatarsal artery on the affected side was measured before operation 3.38 (1.33, 7.56) ml/min, 1 week after operation 4.19(2.84, 11.48) ml/min and 1 month after operation 3.72 (2.52, 11.40) ml/min, with statistically significant difference (χ 2=9.46, P=0.009). There were statistically significant differences in blood flow at 1 week and 1 month after operation compared with that before operation ( P=0.033, P=0.003). The vascular index at the beginning of the first dorsal metatarsal artery on the affected side was 3.84±3.60, 6.51±4.92 and 6.82±5.36 before operation, 1 week and 1 month after operation, respectively, and the differences were statistically significant( F=4.35, P=0.031). The vascular index in the first week after operation was significantly higher than that before operation ( P=0.026). Up to the last follow-up, the number of new collaterals in 18 patients was 4.5 (2, 8), which was significantly different from 1 (0, 2) before operation ( Z=-3.57, P=0.001). In total, the length of 18 new blood vessels in 9 patients was longer than that before operation, and the establishment of grade 2 and grade 3 branches were observed in 5 patients. The superficial subcutaneous vessels were showed more clarity than that before surgery, and there was collateral circulation on the opposite side. Conclusion:SMI objectively reflects the changes of hemodynamics and microcirculation of patients after tibial transverse bone transport, and helps clinical preliminary predict the prognosis of patients and adjust individual treatment plan according to blood perfusion in time.