Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

OBJECTIVE: To investigate the correlation between the anterior talofibular ligament (ATFL) injury and the pathological changes of the anterior tibiotalar fat pad (ATFP) based on MRI. METHODS: The clinical and imaging data of 217 patients with ankle sprain who met the selection criteria between January 2019 and March 2024 were retrospectively analyzed. There were 113 males and 104 females with an average age of 38.2 years ranging from 18 to 60 years. Patients were divided into mild group ( n=106), moderate group ( n=63), and severe group ( n=48) according to the degree of ATFL injury. There was no significant difference in gender, side, and body mass index among the 3 groups ( P>0.05). The age of the mild group was significantly older than that of the moderate and severe groups ( P<0.05). The imaging parameters including the longest and shortest sagittal axis, the largest thickness, the longest and shortest transverse axis, the ATFP area, the area of ATFP high-signal region, and the anterior distal tibial angle (ADTA) were measured according to the MRI and X-ray films of patients. According to the morphology of ATFP, the patients were divided into type Ⅰ ( n=128), type Ⅱ ( n=73), and type Ⅲ ( n=16) based on the severity of the lesions. The distribution of ATFP types, ATFP area, area of ATFP high-signal region, and the ratio of area of ATFP high-signal region to ATFP area at the same level were statistically analyzed and compared among different ATFL injury groups. Additionally, radiographic parameters were compared across different ATFP types. Spearman rank correlation analysis was used to assess the relationships between ATFP area, area of ATFP high-signal region, and the ratio of area of ATFP high-signal region to ATFP area at the same level with patient baseline data. Through analysis of the area under curve (AUC) of ROC, optimal variables were selected for quantification to predict ATFL injury. RESULTS: There were significant differences in ATFP types among different ATFL injury groups ( P<0.05). The mild group had a higher proportion of type Ⅰ, the moderate group had a higher proportion of type Ⅱ, and the severe group had higher proportions of both typeⅡ and type Ⅲ. No significant difference was found in ATFP area among the different ATFL injury groups ( P>0.05). However, the area of ATFP high-signal region and the ratio of area of ATFP high-signal region to ATFP area at the same level were significantly lower in the mild group compared to the moderate and severe groups ( P<0.05). Except for the longest sagittal axis, maximum thickness, and longest transverse axis, which were significantly smaller in ATFP types Ⅱ and Ⅲ compared to type Ⅰ ( P<0.05), there was no significant difference in the remaining radiographic parameters among the different ATFP types ( P>0.05). Spearman rank correlation analysis revealed that ATFP area was negatively correlated with patient gender ( P<0.05), while area of ATFP high-signal region and the ratio of area of ATFP high-signal region to ATFP area at the same level were negatively correlated with patient age ( P<0.05). Through analysis of the AUC for the response variable ATFP injury, the combined diagnostic AUC of ROC for the reciprocal of the maximum thickness and the reciprocal of the area of ATFP high-signal region was 0.839 (asymptotic P<0.001). The corresponding cutoff value when the Youden index reached its maximum was 0.570 3. CONCLUSION As the severity of ATFL injury increases, the ATFP undergoes gradual morphological and functional changes. Classification based on ATFP types can assist in assessing the level of ATFL injury, thereby aiding in the prevention of post-traumatic osteoarthritis.
Humans ; Male ; Female ; Adult ; Magnetic Resonance Imaging/methods* ; Middle Aged ; Retrospective Studies ; Adipose Tissue/pathology* ; Adolescent ; Young Adult ; Lateral Ligament, Ankle/diagnostic imaging* ; Ankle Injuries/pathology*

This study aimed to explore the effects of akebiaquinata and dandelion extracts in impro-ving intestinal redox homeostasis in weaned rabbits.In the trial,120 35-day-old Ira rabbits weig-hing(1.22±0.08)kg were randomly divided into 4 groups according to the two-factor design,namely group C(basal diet),group D(basal diet+0.5％dandelion extract),group A(basal diet+0.5％akebiaquinata extract),and group DA(basal diet+0.5％dandelion extract+0.5％akebia-quinata extract),with 10 replicates in each group.The adapt period was one week and the experi-mental period was four weeks.At the last day,serum,liver tissue,jejunum and ileal mucosa samples were collected and stored for measurement.The results showed that:(1)First week,the average daily weight gain of group C was significantly lower than that of group D and group A(P＜0.05),and the feed weight ratio was significantly higher than that of group D and group A(P＜0.05).(2)The content of reactive oxygen species(ROS)in liver and serum was significantly reduced in akebiaquinata extract(P＜0.01),and the content of serum ROS in dandelion extract was significantly reduced(P＜0.01),and there were significant and extremely significant interac-tions in liver and serum,respectively.Extracts of akebiaquinata and dandelion were effective in re-ducing the levels of oxidative damage markers in tissues and serum,but increasing the content of malondialdehyde in liver tissues.(3)Akebiaquinata extract significantly increased the activity of glutathione peroxidase(GSH-Px)and total antioxidant capacity(T-AOC)in serum(P＜0.01),and significantly reduced the activity of T-AOC in liver(P＜0.01)and superoxide dismutase in je-junum and liver(P＜0.05).Dandelion extract significantly increased the activity of T-AOC in ser-um and GSH-Px in jejunum(P＜0.05).The extracts of akebiaquinata and dandelion had a signifi-cant interaction effect on peroxidase in serum(P＜0.05).(4)The expression of Kelch-like ECH-as-sociated protein 1(Keap1)and NAD(P)H:quinone oxidoreductase 1(NQO1)genes in the jejunum was significantly and extremely significantly reduced by akebiaquinata extract.The extracts of ake-biaquinata and dandelion had significant interaction effects on ileal NQO1,Heme oxygenase1 and Superoxide dismutase 2(P＜0.05)and Keap1(P＜0.01).The expression of NQO1 gene in liver tis-sue was significantly reduced by akebiaquinata extract(P＜0.05).Dandelion and Akebiaquinata ex-tracts can reduce the content of reactive oxygen species in vivo and alleviate oxidative damage.At the same time,dandelion and akebiaquinata extract can work together to regulate antioxidant gene expression and antioxidant enzyme activity through the Nrf2-Keap1 signaling pathway to maintain intestinal redox homeostasis and relieve intestinal oxidative stress.

OBJECTIVE: To investigate ideal screw implant angle in reconstruction of tibiofibular syndesmosis injury by using a biomechanical test. METHODS: A total of 24 ankle specimens from adult cadavers were used as the tibiofibular syndesmosis injury model. According to the angle of screw placement, the tibiofibular syndesmosis injury models were randomly divided into groups A (0°), B (10°-15°), C (20°-25°), and D (30°-35°), and the screws were placed at a level 2 cm proximal to the ankle joint. The displacement of fibula was measured by biomechanical testing machine at neutral, dorsiflexion (10°), plantar flexion (15°), varus (10°), and valgus (15°) positions, with axial load of 0-700 N (pressure separation test). The displacement of fibula was also measured at neutral position by applying 0-5 N·m torque load during internal and external rotation (torsional separation test). RESULTS: In the pressure separation test, group C exhibited the smallest displacement under different positions and load conditions. At neutral position, significant differences were observed ( P<0.05) between group A and group C under load of 300-700 N, as well as between group B and group C under all load conditions. At dorsiflexion position, significant differences were observed ( P<0.05) between group A and group C under load of 500-700 N, as well as between groups B, D and group C under all load conditions, and the displacements under all load conditions were significantly smaller in group A than in group B ( P<0.05). At plantar flexion position, significant differences were observed ( P<0.05) between group D and group C under all load conditions. At valgus position, significant differences were observed ( P<0.05) between group A and group C under load of 400-700 N, as well as between groups B, D and group C under all load conditions. In the torsional separation test, group C exhibited the smallest displacement and group B had the largest displacement under different load conditions. During internal rotation, significant differences were observed ( P<0.05) between group B and group C under all load conditions, as well as between group D and group C at load of 3-5 N·m. During external rotation, significant differences were observed between groups B, D and group C under all load conditions ( P<0.05). No significant difference was detected between groups at the remaining load conditions ( P>0.05). CONCLUSION The ideal screw implant angle in reconstruction of tibiofibular syndesmosis injury was 20°-25°, which has a small displacement of fibula.
Humans ; Bone Screws ; Biomechanical Phenomena ; Fibula/injuries* ; Fracture Fixation, Internal/methods* ; Adult ; Ankle Joint/surgery* ; Ankle Injuries/surgery* ; Tibia/surgery* ; Male ; Range of Motion, Articular ; Weight-Bearing ; Female ; Cadaver ; Plastic Surgery Procedures/methods*

Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH₂) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH₂) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.

Defining and visualizing the three-dimensional (3D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography (SR-μCT). In situ formed 3D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral "roadways". Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed 3D microstructures, a "subterranean river model" for the drug release mechanism has been defined to explain the drug release mechanism.

The antimicrobial peptide APKGVQGPNG (named YD), a natural peptide originating from Bacillus amyloliquefaciens CBSYD1, exhibited excellent antibacterial and antioxidant properties in vitro. These characteristics are closely related to inflammatory responses which is the central trigger for liver fibrosis. However, the therapeutic effects of YD against hepatic fibrosis and the underlying mechanisms are rarely studied. In this study, we show that YD improved liver function and inhibited the progression of liver fibrosis by measuring the serum transaminase activity and the expression of α-smooth muscle actin and collagen I in carbon tetrachloride-induced mice. Then we found that YD inhibited the level of miR-155, which plays an important role in inflammation and liver fibrosis. Bioinformatics analysis and luciferase reporter assay indicate that Casp12 is a new target of miR-155. We demonstrate that YD significantly decreases the contents of inflammatory cytokines and suppresses the NF-κB signaling pathway. Further studies show that transfection of the miR-155 mimic in RAW264.7 cells partially reversed the YD-mediated CASP12 upregulation, the downregulated levels of inflammatory cytokines, and the inactivation of the NF-κB pathways. Collectively, our study indicates that YD reduces inflammation through the miR-155–Casp12–NF-κB axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.

Objective:To explore the role of epithelial-mesenchymal transition(EMT) in fusion of the secondary palatal shelves to form the intact secondary palate induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).Methods:Twelve C57BL/6 J pregnant mice on gestation day (GD) 10.5 were divided into two groups: one group was conducted through gastric tubes with one dose of 28 μg/kg TCDD (experimental group) and the other group was operated through gastric tubes with equal volume corn oil (control group). Embryos were removed by cesarean section from pregnant mice during the palatal formation stage (GD 15.5) and the morphology of palatal tissue was observed. Primary media edge epithelial(MEE) were divided into experimental group and control group. MEE were treated with medium containing TCDD, 5 nmol/L, 10 nmol/L, 20 nmol/L and normal medium respectively. The expression of cytokeratin 19(CK-19) protein and vimentin protein in MEE were detected by immunofluorescence laser confocal microscopy and Western blotting after 72 hours. Statistical comparisons were made using one-way ANOVA.Results:A total of 36 fetuses were obtained in the experimental group, including 3 dead fetuses and absorbed fetuses. The incidence of cleft palate was 100% (33/33); the incidence of complete cleft palate was 84.8% (28/33), and the incidence of partial cleft palate was 15.2% (5/33); 40 fetuses were obtained in the control group, including 2 dead fetuses and resorbed fetuses, and the incidence of cleft palate was 0 (0/38). After 72 hours, the shape of MEE changed from uniform pebble-like to star-like or irregular shape with pseudopodia. The expressions of CK-19 protein were(0.739 ± 0.120, 0.483 ± 0.023, 1.007 ± 0.109, 1.086 ± 0.145) and fluorescence intensities were (53.384±5.785, 36.818 ± 8.250, 64.575±8.323, 76.898 ± 3.711) in control group and TCDD (5 nmol/L), TCDD (10 nmol/L) and TCDD (20 nmol/L) groups, respectively. The expressions of vimentin protein were (0.527 ± 0.112, 0.781 ± 0.095, 0.284 ± 0.046, 0.216 ± 0.040) and fluorescence intensities were (63.672±6.135, 82.632 ± 4.474, 52.608±7.525, 42.664 ± 7.659). Compared with the control group, the low-dose experimental group (5 nmol/L) had a decrease in CK-19 and an increase in vimentin; the high-dose experimental group (10 nmol/L, 20 nmol/L) had an increase in CK-19 and a decrease in vimentin, and the expression difference was statistically significant ( P<0.05), while there was no statistical significance among high-dose groups ( P>0.05). Conclusions:EMT process of MEE was identified in vitro and was a spontaneous procedure. TCDD-induced cleft palate may be related to the inhibition of the EMT process in MEE and with the increased dose of TCDD, the effects of EMT inhibiton were sustainable.

Objective:To explore the role of epithelial-mesenchymal transition(EMT) in fusion of the secondary palatal shelves to form the intact secondary palate induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).Methods:Twelve C57BL/6 J pregnant mice on gestation day (GD) 10.5 were divided into two groups: one group was conducted through gastric tubes with one dose of 28 μg/kg TCDD (experimental group) and the other group was operated through gastric tubes with equal volume corn oil (control group). Embryos were removed by cesarean section from pregnant mice during the palatal formation stage (GD 15.5) and the morphology of palatal tissue was observed. Primary media edge epithelial(MEE) were divided into experimental group and control group. MEE were treated with medium containing TCDD, 5 nmol/L, 10 nmol/L, 20 nmol/L and normal medium respectively. The expression of cytokeratin 19(CK-19) protein and vimentin protein in MEE were detected by immunofluorescence laser confocal microscopy and Western blotting after 72 hours. Statistical comparisons were made using one-way ANOVA.Results:A total of 36 fetuses were obtained in the experimental group, including 3 dead fetuses and absorbed fetuses. The incidence of cleft palate was 100% (33/33); the incidence of complete cleft palate was 84.8% (28/33), and the incidence of partial cleft palate was 15.2% (5/33); 40 fetuses were obtained in the control group, including 2 dead fetuses and resorbed fetuses, and the incidence of cleft palate was 0 (0/38). After 72 hours, the shape of MEE changed from uniform pebble-like to star-like or irregular shape with pseudopodia. The expressions of CK-19 protein were(0.739 ± 0.120, 0.483 ± 0.023, 1.007 ± 0.109, 1.086 ± 0.145) and fluorescence intensities were (53.384±5.785, 36.818 ± 8.250, 64.575±8.323, 76.898 ± 3.711) in control group and TCDD (5 nmol/L), TCDD (10 nmol/L) and TCDD (20 nmol/L) groups, respectively. The expressions of vimentin protein were (0.527 ± 0.112, 0.781 ± 0.095, 0.284 ± 0.046, 0.216 ± 0.040) and fluorescence intensities were (63.672±6.135, 82.632 ± 4.474, 52.608±7.525, 42.664 ± 7.659). Compared with the control group, the low-dose experimental group (5 nmol/L) had a decrease in CK-19 and an increase in vimentin; the high-dose experimental group (10 nmol/L, 20 nmol/L) had an increase in CK-19 and a decrease in vimentin, and the expression difference was statistically significant ( P<0.05), while there was no statistical significance among high-dose groups ( P>0.05). Conclusions:EMT process of MEE was identified in vitro and was a spontaneous procedure. TCDD-induced cleft palate may be related to the inhibition of the EMT process in MEE and with the increased dose of TCDD, the effects of EMT inhibiton were sustainable.

Objective To observe the efficacy and safety of intravitreal injection of ranibizumab in the treatment of retinopathy of prematurity (ROP).Methods Data from 49 consecutive ROP patients (95 eyes) including type Ⅰ pre-threshold,threshold and aggressive posterior ROP who had received anti-VEGF treatment for the first time in our hospital from June 2014 to August 2015 were collected.60 eyes from the 95 eyes were confined as the zone Ⅰ disease group,while the remaining 35 eyes as zone Ⅱ disease group.The difference of birth weight,gestational age,corrected gestational age,treatment effects,recurrence and re-treatment time between two groups were compared.0.025 mL ranibizumab (10 mg · mL-1) was injected through 1.5 mm puncture after corneal limbus by using 30G 1 mL injection syringe.At the end of the injection,tobramycin and dexamethasone ophthalmic ointment eye bag was used.After the injection of 3 days,the portable slit lamp and tonometer were used to observe the intraocular pressure,intraocular hemorrhage and endophthalmitis.The indirect ophthalmoscope was used to observe the retinal vascular tortuosity and ridge regression of lesion expansion at 1 week after treatment.At the same time,the systemic adverse reactions related to treatment were observed.Results After receiving ranibizumab treatment for the first time,93 eyes (95.9％) exhibited ROP regression after single injection,including 58 eyes in zone Ⅰ disease group,35 eyes in zone Ⅱ disease group.There was no statistical difference between two groups (P ＞ 0.05).22 eyes required additional anti-VEGF injection or laser treatment for ROP recurrence,including 17 eyes in zone Ⅰ disease group,5 eyes in zone Ⅱ disease group.There was statistical difference between two groups (P ＜0.05).The time from recurrence to re-treatment was (6.50 ±2.54) weeks,which in zone Ⅰ disease group was (6.44 ± 2.74) weeks and in zone Ⅱ disease group was (6.67 ± 2.31)weeks,there was no statistical difference between two groups (P ＞ 0.05).No local or systemic adverse events associated with the treatment or drug was observed within the following period.Conclusion Intravitreal injection of ranibizumab is an effective and well tolerated method for zone Ⅰ and zone Ⅱ ROP,but the recurrence rate is high.There Is no local or systemic adverse events associated with the treatment or drug.