Jiawei Yanghe Decoction suppresses breast cancer by regulating immune responses via JAK2/STAT3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Yanghe Decoction (JWYHD) is a widely used traditional Chinese medicine prescription in the clinical setting for the treatment of autoimmune diseases. Many studies showed that JWYHD has anti-tumor activities in cell and animal models. However, the anti-breast cancer effects of JWYHD and the underlying mechanisms of action remain unknown. AIM OF STUDY: This study aimed to determine the anti-breast cancer effect and reveal the underlying mechanisms of action in vivo, in vitro and in silico. MATERIALS AND METHODS: Orthotopic xenograft breast cancer mouse model and inflammatory zebrafish model were used to observe the anti-tumor effect and immune cell regulation of JWYHD. Moreover, the anti-inflammatory effect of JWYHD were evaluated by the expression of RAW 264.7 cells. JWYHD active ingredients were obtained by UPLC-MS/MS and potential targets were screened by network pharmacology. The therapeutic targets and signaling pathways predicted by computer were assessed by Western blot, real-time PCR (RT-PCR), immunohistochemistry (IHC) staining, and Enzyme-linked immunosorbent assays (ELISA) to explore the therapeutic mechanism of JWYHD against breast cancer. At last, Colivelin and Stattic were used to explore the effect of JWYHD on JAK2/STAT3 pathway. RESULTS: JWYHD significantly decreased the tumor growth in a dose-dependent manner in the orthotopic xenograft breast cancer mouse model. Flow cytometry and IHC results indicated that JWYHD decreased the expressions of M2 macrophages and Treg while increasing M1 macrophages. Meanwhile, ELISA and Western blot results showed a decrease in IL-1ß, IL-6, TNFα, PTGS2 and VEGFα in tumor tissue of JWYHD groups. The results were also verified in LPS-induced RAW264.7 cells and zebrafish inflammatory models. TUNEL assay and IHC results showed that JWYHD significantly induced apoptosis. Seventy-two major compounds in JWYHD were identified by UPLC-MS/MS and Network pharmacology. It was found that the significant binding affinity of JWYHD to TNFα, PTGS2, EGFR, STAT3, VEGFα and their expressions were inhibited by JWYHD. IHC and Western blot analysis showed that JWYHD could decrease the expression of JAK2/STAT3 pathway. Furthermore, Colivelin could reverse the decrease effect of JWYHD in vitro. CONCLUSION: JWYHD exerts a significant anti-tumor effect mainly by inhibiting inflammation, activating immune responses and inducing apoptosis via the JAK2/STAT3 signaling pathway. Our findings provide strong pharmacological evidence for the clinical application of JWYHD in the management of breast cancer.

[Effect of titanium nitride coatings with different thickness on microhardness and cutting efficiency of nickel-titanium instruments].

PURPOSE: To investigate the effect of titanium nitride (TiN) coatings with different thicknesses on microhardness and cutting efficiency of nickel-titanium (NiTi) instruments, and to provide a basis for improving the efficiency of clinical root canal preparation. METHODS: Fifteen KV4 NiTi alloy sheets and sixty KV4 rotary NiTi files were selected and randomly divided into 5 groups: uncoated group, coating 1 h group, coating 2 h group, coating 3 h group and coating 4 h group. A layer of TiN coatings of different thicknesses was prepared on the surface of the coated groups by controlling the deposition time. The film thickness of each group was measured by scanning electron microscopy (SEM). The microhardness of each group of NiTi alloy sheets was measured by a Vickers hardness tester. Sixty transparent resin modules were selected and each resin module was prepared with one NiTi file. The cutting efficiency of each group was measured by the weight loss method. SEM was used to examine the surface of NiTi instruments in 5 groups before and after preparation. One-way variance analysis was used to determine the statistical differences with SPSS 22.0 software package. RESULTS: With the increase of the thickness of titanium nitride coating, the microhardness of NiTi alloy gradually increased(P＜0.05). With the increase of the thickness of titanium nitride coating, the cutting efficiency of NiTi instrument was improved, and the cutting efficiency was the largest when the coating thickness was 860 nm(P＜0.05). The surface morphology of the coated group was better than that of the uncoated group. CONCLUSIONS: The thickness of TiN coating affects microhardness and cutting efficiency of the nickel-titanium instruments, the microhardness and cutting ability enhanced as the thickness increased. If the thickness is too large, the cutting efficiency will be reduced.

[Treatments of second mesiobuccal canals in maxillary permanent molar: a report of 2 cases].

With the increasing maturation of 3D printing technology, as well as its application in various industries, investigation of 3D printing technology into clinic medical education becomes an important task of the current medical education. The teaching content of oromaxillofacial head and neck surgical oncology is complicated and diverse, making lower understanding/memorizing efficiency and insufficient skill training. To overcome the disadvantage of traditional teaching method, it is necessary to introduce 3D printing technique into teaching of oromaxillofacial head and neck surgical oncology, in order to improve the teaching quality and problem solving capabilities, and finally promote cultivation of skilled and innovative talents.

[Expression of Wnt5a in chronic apical periodontitis and its clinical significance].

PURPOSE: To detect the expression of Wnt5a in lesions of chronic apical periodontitis and determine the relationship between expression of Wnt5a and inflammation degree. METHODS: Ten patients with chronic apical periodontitis and 5 healthy controls were enrolled in this study. According to the inflammatory cell infiltration, the specimens were divided into 2 groups: severe inflammation group and mild inflammation group. The expression of Wnt5a was measured by real-time PCR (RT-PCR) and immunohistochemical analysis in the lesions of chronic apical periodontitis. The amount of Wnt5 expression was assayed and compared in different inflammation levels. Statistical analysis was performed using SPSS 13.0 software package. RESULTS: Wnt5a was detected in both groups. Expression of Wnt5a mRNA in patients were significantly higher than the controls (P<0.05). According to inflammation level, the positive expression rate of Wnt5a in severe inflammation group was significantly higher than the controls (P<0.01), and Wnt5a positive expression in mild inflammation group was also significantly higher than the controls (P<0.05). The expression of Wnt5a was significantly different between severe inflammation group and mild inflammation group (P<0.05). CONCLUSIONS: The expression of Wnt5a increases as the severity of tissue inflammation increases, which indicates that Wnt5a plays an important role in the development of chronic apical periodontitis.

Evaluation of the stress distribution change at the adjacent facet joints after lumbar fusion surgery: a biomechanical study.

Spinal fusion surgery has been widely applied in clinical treatment, and the spinal fusion rate has improved markedly. However, its postoperative complications, especially adjacent segment degeneration, have increasingly attracted the attention of spinal surgeons. The most common pathological condition at adjacent segments is hypertrophic degenerative arthritis of the facet joint. To study the stress distribution changes at the adjacent facet joint after lumbar fusion with pedicle screw fixation, human cadaver lumbar spines were used in the present study, and electrical resistance strain gauges were attached on L1-L4 articular processes parallel or perpendicular to the articular surface of facet joints. Subsequently, electrical resistance strain gauge data were measured using anYJ-33 static resistance strain indicator with three types of models: the intact model, the laminectomy model, and the fusion model with pedicle screw fixation. The strain changes in the measurement sites indirectly reflect the stress changes. Significant differences in strain were observed between the normal and laminectomy state at all facet joints. Significant differences in strain were observed between the normal and the pedicle screw fixation fusion state at the L1/2 and L3/4 facet joints. The increased stress on the facet joints after lumbar fusion with pedicle screw fixation may be the cause of adjacent segment degeneration.

Biomechanical analysis of four types of internal fixation in subtrochanteric fracture models.

OBJECTIVE: To compare the biomechanical properties of four types of internal fixation (proximal femoral nail [PFN], dynamic hip screw [DHS], dynamic condylar screw [DCS], and proximal femoral locking plate [PFLP]) for different types of subtrochanteric fractures. METHODS: Thirty-two antiseptic femurs were randomly divided into four groups. After internal fixation had been implanted, different types of subtrochanteric fracture models were produced and each tested under vertical, torsional and vertical damage loads. RESULTS: The stiffness ratio of PFN in each fracture model and failure load were the highest in the four groups; however, the torsional stiffness ratio was the lowest. Tension strain ratios of DHS and DCS on the lateral side became compression strain ratios with restoration of the medial fragment. The stiffness ratio of DHS was lower than PFLP in each fracture model, torsional stiffness ratio was the highest in fracture models II to V and the failure load was lower only than PFN. The stiffness ratio and failure load of DCS were both the lowest, torsional stiffness ratio was similar to PFLP's in fracture models II to V. The stiffness ratio of PFLP was only lower than PFN's in each fracture model, but the failure load was lower than DHS's. CONCLUSION: Four types of internal fixation achieve better stabilities for type I subtrochanteric fractures. PFN and PFLP produce reliable stability in type IIIA subtrochanteric fractures. If the medial buttress is restored, DCS can be considered. For type IV subtrochanteric fractures, only PFN provides stable fixation. PFLP is suitable for comminuted fractures with large fragments.

A biomechanical study of the recovery in spinal stability of flexion/extension and torsion after the resection of different posterior lumbar structures in a sheep model.

Posterior lumbar structures are vital for spinal stability, and many researchers thought that laminectomy and facetectomy would lead to severe spinal instability. However, because living organisms have compensatory repair capacities, their long-term condition after injuries may change over time. To study the changes in the lumbar biomechanical stability of flexion/extension and torsion at different time points after the resection of various posterior structures, as well as to assess the capacity for self-healing, sheep that had undergone laminectomy or facetectomy were used as an experimental animal model. The injured sheep models included three groups: laminectomy only, laminectomy plus left total facetectomy, and laminectomy plus bilateral facetectomy. Eight nonoperative sheep were used as the control group. At 0, 6, 12, 24, and 36 weeks after injury, the lumbar specimens were harvested for biomechanical testing using the Instron 8874 servohydraulic biomechanical testing system. The changes in the injured lumbar spine were also analyzed through radiological examination. The lumbar stability in flexion/extension and torsion was severely decreased after the three types of surgery. After 6 weeks, the flexion/extension mechanical parameters recovered substantially; each parameter had returned to normal levels by 12 weeks and exceeded the intact group by 24 and 36 weeks. Torsional stiffness also recovered gradually over time. All injury groups demonstrated decreased intervertebral space and degeneration or even fusion in the small joints of the surgical segment or in adjacent segments. These results indicate that the body has the ability to repair the mechanical instability to a certain extent.

[Comparative study on the shaping ability of canals with 2 new nickel- titanium rotary instruments].

PURPOSE: To compare the shaping ability of two nickel-titanium rotary systems: Mtwo and K3. METHODS: Thirty-six mesio-buccal root canals of maxillary first molars were divided into two groups: group A(> or =20> or =) and group B(<20 degrees ),according to the angle of the canal. Then, each group was randomly divided into two subsets and prepared by Mtwo,K3, respectively. All root canals were injected with the contrast medium and digital images of all canals were recorded before and after instrumentation. The computer assistant analyze image software was used to form the geometrical central line of pre-instrumented canals. Then the central line was imaged to the post-instrumented canals. The canal transportation and the decrease of curvature were measured. All the data was analyzed with SPSS11.0 software package. RESULTS: Difference between groups was compared using t test.When the curvature of canal > or =20 degrees ,the transportation at the beginning of the curvature and the decrease of curvature of Mtwo were significantly less than those of K3(P<0.05).When the curvature of canal <20 degrees there was no significant difference between Mtwo and K3 in the transportation and decrease of curvature(P>0.05). CONCLUSIONS: Both Mtwo and K3 systems show good preservation of the original geometry of the root canals, the Mtwo system can better preserve original curvature of canals, when the curvature of canal is larger than 20 degrees .

[A study on acquired acid resistance of enamel and dentine irradiated by Er, Cr: YSGG laser in vitro].

OBJECTIVE: To evaluate the acid resistance of enamel and dentin irradiated by Er, Cr: YSGG laser to artificial caries formation in vitro. METHODS: Enamel and dentin samples were irradiated with Er, Cr: YSGG laser at 6 W or 4 W for 6 second, respectively. Every sample was immersed in 3 ml of lactic demineralization solution at pH 4.8 and incubated at 37 degrees C for 24 hours. The parts per million of calcium ion of each solution was measured by atomic absorption spectrophotometry, the quantities of calcium and phosphate on the surface of enamel and dentin sample were examined by SED-X and the ultrastructure was investigated by SEM. RESULTS: In the enamel and dentin samples, the dissolved Ca(2+) concentration in laser group were significantly decreased compared with that of the control group (P < 0.05). The quantities of Ca (weight%) in enamel and dentin were significantly higher in the laser group than in the control group (P < 0.05). The content of P was increased in dentin and enamel samples, but only the increase in enamel sample was significant (P < 0.05). In both samples, no significant changes on Ca/P weight ratio were found between the groups. The irradiated enamel and dentin surface lacked a smear layer and showed various patterns of microirregulation with a scaly appearance, the openings of dentinal tubules were clearly visible, but no melting or carbonization was observed. CONCLUSION: Er, Cr: YSGG laser irradiation is effective for increasing acid resistance of dental hard tissue and does not cause thermal side effect.