[Purpose]To evaluate the liver and kidney safety of traditional Chinese medicine(TCM)compounds in the treatment of gastric cancer.[Methods]The clinical data of gastric cancer patients who attended in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2012 to February 2022 were collected.The results of liver and renal func-tion tests were rated according to National Cancer Institute-Common Terminology Criteria for Ad-verse Events(NCI-CTCAE)V5.0.The patients were divided into 4 groups:TCM group,TCM+chemotherapy/targeted/antivascular therapy group,TCM+TCM preparation group and TCM+chemotherapy/targeted/antivascular therapy+TCM preparation group,and the effects of TCM on liver and renal functions were analyzed.[Results]A total of 7 943 patients were included in the analysis,of which 2 941 cases receiving TCM ≥12 months,1 468 months ≥36 months,and 687 months≥60 months.The highest incidence rate of liver function abnormality was 13.71％,the highest in-cidence rate of grade 3/4 abnormality was 2.58％;the highest incidence of creatinine abnormality was 2.32％,the highest incidence rate of grade 3/4 abnormality was 0.37％in patients with differ-ent duration of taking TCM.Most of liver and renal function abnormalities occurred in the early stage of drug taking.The incidence of liver and renal function abnormalities in the TCM group was lower than that of the other three groups.The incidence of grade 3/4 abnormality for direct biliru-bin(DBIL)in the TCM group was 0.14％,for aspartate transaminase(AST)was 0.11％,for alka-line phosphatase(ALP)was 0.16％,for alanine aminotransferase(ALT)was 0.06％and for total bilirubin(TBIL)was 0.07％,and there was no grade 3/4 creatinine abnormality observed.The ab-normal liver and renal function indexes were not increased with the increase of the length of herbal medicine taking.[Conclusion]The study shows that long term taking TCM drugs and stan-dardized prescriptions for gastric cancer patients are safe.

Application of invisible orthodontic appliances in the treatment of adult skeletal malocclusions,especially in the cases requiring tooth extraction,has always been one of the challenges in invisible orthodontic technology.Our department received a 30-year-old female patient in March 2019;the patient presented with complaints of"crooked teeth and protruding mouth,"seeking orthodontic treatment to improve her facial profile.The patient had bilateral distal molar relationship,proclined maxillary and mandibular anterior teeth,and deep overjet;radiographic examination revealed an ANB angle of 6.2°,indicating a skeletal Class Ⅱ malocclusion.By extracting four first premolars and using four miniscrews,after 20 months of treatment,the extraction spaces were fully closed,the dental arch was aligned,and the occlusal relationship was favorable;the anterior teeth were retracted,the mandible showed a reverse rotation,and the soft tissue profile was significantly improved.Application of invisible orthodontic appliances in conjunction with miniscrews anchorage can achieve good three-dimensional control of tooth movement in adult extraction cases,providing a reference for clinical practitioners treating such patients.

Objective:To investigate the effects of Juglone on the apoptosis of osteosarcoma(OS)cells(U2OS and MG63 cells)through the cysteinyl aspartate specific proteinase-3(Caspase-3)/gasdermin E(GSDME)-mediated pyroptosis pathway.Methods:The U2OS and MG63 cells were cultured in vitro and divided into control group,different concentrations(5,10 and 20 μmol·L-1)of Juglone groups and Caspase-3 inhibitor Z-DEVD-FMK group(10 μmol·L-1 Juglone+30 μmol·L-1 Z-DEVD-FMK).The survival rates of cells in various groups were assessed by cell counting kit-8(CCK-8)assay,and the apoptotic rates were detected by flow cytometry.Lactate dehydrogenase(LDH)release assay was used to measure the release rates of LDH from the cells.Western blotting method was used to detect the expression levels of apoptosis-related proteins including B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),cleaved-Caspase-3 and poly(ADP-ribose)polymerase(PARP)and pyroptosis-related proteins including GSDME full form(GSDME-F)and GSDME N-terminal(GSDME-N).The levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)in the cell supernataut in various groups were measured by enzyme-linked immunosorbent assay(ELISA)method.Results:Compared with control group,the survival rates of cells in 5,10,and 20 μmol·L-1Juglone groups were significantly decreased(P＜0.05 or P＜0.01),and the 50％inhibitory concentration(IC50)values of U2OS cells and MG63 cells were 8.4 and 10.2 μmol·L-1,respectively.Compared with control group,the apoptotic rates and LDH release rates of U2OS and MG63 cells in 5 and 10 μmol·L-1Juglone groups were significantly increased(P＜0.05 or P＜0.01).Compared with control group,the expression levels of Bax,cleaved-Caspase-3,and cleaved-PARP proteins in 5 and 10 μmol·L-1 Juglone groups were significantly increased(P＜0.01),while the expression levels of Bcl-2 protein were significantly decreased(P＜0.01).Compared with control group,the levels of IL-1β and IL-18 in cell supernatant in 5 and 10 μmol·L-1Juglone groups were increased(P＜0.01).Compared with control group,the expression levels of cleaved-Caspase-3 and GSDME-N proteins in 5 and 10 μmol·L-1 Juglone groups were significantly increased(P＜0.01),while there was no difference in the expression level of GSDME-F protein(P＞0.05).Compared with 10 μmol·L-1 Juglone group,the expression levels of cleaved-Caspase-3 and GSDME-N in Z-DEVD-FMK group were significantly decreased(P＜0.01),while there was no difference in the expression level of GSDME-F protein(P＞0.05).Conclusion:Juglone can induce the apoptosis of U2OS and MG63 cells and cause the Caspase-3/GSDME-mediated pyroptosis.

Skeletal class Ⅱ malocclusion is characterized by maxillary protrusion,mandibular retrognathia,or a combination of both,and often accompanied by vertical dimensional discrepancies;treatment is complex,and combined orthodontic-orthognathic surgery is needed for the adult patients.Clear aligner therapy has gradually been applied in complex orthodontic cases.However,limited cases have been reported domestically and internationally regarding the application of clear aligner therapy combined with orthognathic surgery.This article presented a case of a patient with skeletal class Ⅱ high-angle malocclusion treated with the combined therapy and analyzed the clinical efficacy of the treatment appraoch to provide reference for the clinical practice.Extraction of impacted wisdom teeth 18,28,38,and 48,as well as orthodontic teeth 15,25,34,and 44,was performed in stages before orthodontic treatment.Clear aligner therapy was used for preoperative orthodontics.In sagittal plane,a super-complete class Ⅱ canine and molar relationship and a 13-14 mm overjet of the anterior teeth were established.The maxillary and mandibular arch morphology was matched horizontally.The orthognathic surgery included maxillary LeFort Ⅰ osteotomy,bilateral sagittal split ramus osteotomy(BSSRO)and chinplasty.Fine occlusal adjustment was conducted after operation.After treatment,the skeletal relationship between upper and lower jaw was corrected to normal;subspinale-nasion-supramental angle(ANB)was improved from 12.3° to 4.7°;the patient established the class Ⅰ canine and molar relationship,with normal overjet and overbite;root parallelism was good and there was no obvious root resorption;the facial soft tissue profile was significantly improved,and nasion-subnasale-pogonion angle(N-Sn-Pg)was improved from 143.9° to 162.8°.The curative effect was stable 1 year after operation.Clear aligner therapy can efficiently complete combined orthodontic and orthodontic surgery in the complex cases.Compared with the fixed appliance,it is more beneficial to the patients'need for beauty and the maintenance of periodontal health.

The patients with skeletal Class Ⅱ high-angle malocclusion are frequently complicated by idiopathic condylar resorption(ICR),which may lead to temporomandibular joint(TMJ)dysfunction and dentofacial deformities.This article reports the diagnosis and treatment process of a 24-year-old female patient with skeletal Class Ⅱ high-angle malocclusion accompanied by ICR.The patient's chief complaints were anterior open bite and TMJ pain,and was diagnosed with ICR through clinical examination and imaging.After stabilizing condylar resorption with occlusal splint therapy,combined orthodontic-orthognathic treatment was performed.The 42-month follow-up revealed:well-aligned dentition with complete closure of diastemas,significant improvement of protrusive facial profile(ANB angle reduced by 4.2°),complete resolution of TMJ pain and clicking,and establishment of stable Class Ⅰ occlusion.Three-dimensional CT demonstrated satisfactory condylar bone remodeling and normalized joint space.Through multidisciplinary treatment,both occlusal function and facial aesthetics were significantly improved.This case demonstrates that orthodontic-orthognathic treatment should be performed after condylar stabilization in ICR patients,and occlusal splint therapy serves as an effective preoperative intervention.

[Purpose]To evaluate the liver and kidney safety of traditional Chinese medicine(TCM)compounds in the treatment of gastric cancer.[Methods]The clinical data of gastric cancer patients who attended in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2012 to February 2022 were collected.The results of liver and renal func-tion tests were rated according to National Cancer Institute-Common Terminology Criteria for Ad-verse Events(NCI-CTCAE)V5.0.The patients were divided into 4 groups:TCM group,TCM+chemotherapy/targeted/antivascular therapy group,TCM+TCM preparation group and TCM+chemotherapy/targeted/antivascular therapy+TCM preparation group,and the effects of TCM on liver and renal functions were analyzed.[Results]A total of 7 943 patients were included in the analysis,of which 2 941 cases receiving TCM ≥12 months,1 468 months ≥36 months,and 687 months≥60 months.The highest incidence rate of liver function abnormality was 13.71％,the highest in-cidence rate of grade 3/4 abnormality was 2.58％;the highest incidence of creatinine abnormality was 2.32％,the highest incidence rate of grade 3/4 abnormality was 0.37％in patients with differ-ent duration of taking TCM.Most of liver and renal function abnormalities occurred in the early stage of drug taking.The incidence of liver and renal function abnormalities in the TCM group was lower than that of the other three groups.The incidence of grade 3/4 abnormality for direct biliru-bin(DBIL)in the TCM group was 0.14％,for aspartate transaminase(AST)was 0.11％,for alka-line phosphatase(ALP)was 0.16％,for alanine aminotransferase(ALT)was 0.06％and for total bilirubin(TBIL)was 0.07％,and there was no grade 3/4 creatinine abnormality observed.The ab-normal liver and renal function indexes were not increased with the increase of the length of herbal medicine taking.[Conclusion]The study shows that long term taking TCM drugs and stan-dardized prescriptions for gastric cancer patients are safe.

Background: Curcumin, the main yellow pigment in turmeric, is a potent anticancer agent. However, its effect on the viability of human prostate cancer (PCa) cells and underlying mechanisms remain unclear. This study aimed to determine the effects of curcumin on the proliferation and glucose metabolism of PCa cells. Methods: Cell viability was measured by MTS assay, and apoptosis was measured by flow cytometry. Glucose metabolism was assessed by measuring glucose intake, lactate production, and adenosine triphosphate content. Western blotting was performed to detect the expression of apoptosis-related proteins. Results: Curcumin treatment significantly reduced the viability of two types of PCa cells. We also found that curcumin increased apoptosis and glycolysis by inhibiting the activities of phosphatidylinositol 3-kinase/protein kinase B and hypoxia-inducible factor-1α. Furthermore, curcumin reduced the expression of ETS-related gene (ERG). However, after the ERG was knocked out, the effects of curcumin treatment were attenuated. Conclusion This study investigated the effects of curcumin on the proliferation and apoptosis of PCa cells, which may be related to the inhibition of glycolysis, and further explored the pathway involved. The subsequent effect on ERG expression indicated that these effects may be related to this oncogene.

OBJECTIVE To characterize the chemical constituents of the cladodes and fruits of Opuntia Milpa Alta by using UPLC-QE-Orbitrap MS, and investigate the antioxidant activity, and explore the relationship between the constituents and biological activity. METHODS The UPLC HSS T3 C18 column(2.1 mm×10 mm, 1.8 μm) was used. Acetonitrile and water with 0.1% formic acid was used for gradient elution at a 0.2 mL·min–1 flow rateas. Heated electrospray ion source was used for primary and secondary mass spectrometry data acquisition in positive and negative ion modes, respectively. Database and literature reports were used to characterize the chemical constituents of the cladodes and fruits of Opuntia Mipa Alta. DPPH radical, hydroxyl radical(·OH) and superoxide anion radical(· ) scavenging ability were used to investigate the antioxidant activities of the cladodes and fruits of Opuntia Milpa Alta. RESULTS A total of 39 compounds were characterized from the cladodes and fruits of Opuntia Milpa Alta, including 22 phenolic compounds, 13 flavonoids and 4 other components. Both cladodes and fruits of Opuntia Milpa Alta had certain antioxidant capacity. The fruits of Opuntia Milpa Alta had better scavenging ability of DPPH than the cladodes, while the cladodes had a slightly stronger scavenging ability of ·OH than the fruits. The scavenging ability of · between cladode peels and fruit peels was not significantly different, and the juice had the strongest scavenging ability of · . The antioxidant activity of Opuntia Milpa Alta was closely related to its rich phenolic acids. CONCLUSION In this study, a rapid, accurate and reliable method is established to identify the chemical constituents of the cladodes and fruits of Opuntia Milpa Alta, which provides scientific basis for the comprehensive development and utilization of Opuntia Milpa Alta.

Objective:To discuss the effect of curcumin on the proliferation,migration,and invasion of the human prostate cancer C4-2 and LNCaP cells,and to clarify its possible mechanism.Methods:The lentiviral transfection system was used to transfect the C4-2 and LNCaP cells,regarded as shCD147-C4-2 group and shCD147-LNCaP group.RNA interference technology was used to prepare the CD147-silenced cells;the cells transfected with an empty vector were regarded as negative control and divided into shNC-C4-2 group(shNC-C4-2 cells)and shNC-LNCaP group(shNC-LNCaP cells).The C4-2 and LNCaP cells at logarithmic growth phase,as well as shCD147-C4-2 and shCD147-LNCaP cells,were treated with 20 μmol·L-1 curcumin.The morphology of the cells in various groups was observed under microscope at 0 and 24 h of treatment;MTT method was used to detect the proliferation activities of the cells in various groups;cell scratch assay was used to detect the migration rates of the cells in various groups;Western blotting method was used to detect the expression levels of apoptosis,invasion,and migration-related proteins in the cells in various groups.Results:Compared with C4-2 group,the expression of CD147 protein in the cells in shCD147-C4-2 group was significantly decreased after CD147 gene silenting.Compared with LNCaP group,the expression level of CD147 protein in the cells in shCD147-LNCaP group was significantly decreased after CD147 gene silenting.Compared with 0 h of treatment,some cells in C4-2 and LNCaP groups after 24 h of treatment with 20 μmol·L-1 curcumin,showed apoptosis signs with the presence of typical apoptotic bodies.The apoptotic phenomena in shCD147-C4-2 and shCD147-LNCaP groups was reduced.The MTT assay results showed that compared with C4-2+0 μmol·L-1 curcumin group,the proliferation activities of the cells in C4-2+20 μmol·L-1 curcumin group,C4-2+40 μmol·L-1 curcumin group,C4-2+60 μmol·L-1 curcumin group,and C4-2+80 μmol·L-1 curcumin group were decreased(P<0.01).Compared with LNCaP+0 μmol·L-1 curcumin group,the proliferation activity of the cells in LNCaP+20 μ mol·L-1 curcumin group,LNCaP+40 μmol·L-1 curcumin group,LNCaP+60 μmol·L-1 curcumin group,and LNCaP+80 μmol·L-1 curcumin group were decreased(P<0.01).Compared with shNC-C4-2 group,the proliferation activity of the cells in shNC-C4-2+20 μmol·L-1 curcumin group was decreased(P<0.01).Compared with shNC-C4-2+20 μmol·L-1 curcumin group,the proliferation activity of the cells in shCD147-C4-2+20 μmol·L-1 curcumin group was increased(P<0.01).Compared with shNC-LNCaP group,the proliferation activity of the cells in shNC-LNCaP+20 μmol·L-1 curcumin group was decreased(P<0.01);compared with shNC-LNCaP+20 μmol·L-1 curcumin group,the proliferation activity of the cells in shCD147-LNCaP+20 μmol·L-1 curcumin group was significantly increased(P<0.01).The cell scratch healing assay results showed that compared with C4-2 group,the migration rates of the cells in C4-2+20 μmol·L-1 curcumin group and C4-2+40 μmol·L-1 curcumin group after 24 h of treatment were decreased(P<0.01);compared with LNCaP group,the migration rates of the cells in LNCaP+20 μmol·L-1 curcumin group and LNCaP+40 μmol·L-1 curcumin group were increased(P<0.01);compared with shNC-C4-2 group,the migration rate of the cells in shNC-C4-2+20 μmol·L-1 curcumin group was decreased(P<0.01);compared with shNC-C4-2+20 μmol·L-1 curcumin group,the migration rate of the cells in shCD147-C4-2+20 μmol·L-1 curcumin group was significantly increased(P<0.05);compared with shNC-LNCaP group,the migration rate of the cells in shNC-LNCaP+20 μmol·L-1 curcumin group was decreased(P<0.01);compared with shNC-LNCaP+20 μmol·L-1 curcumin group,the garation rate of the cells in shCD147-LNCaP+20 μmol·L-1 curcumin group was significantly increased(P<0.05).The Western blotting results showed that compared with C4-2 group,the expression levels of Bcl-2-associated X protein(Bax),cleaved Caspase-3,and poly ADP-ribose polymerase 1(PARP1)proteins in the cells in C4-2+20 μmol·L-1 curcumin group and C4-2+40 μmol·L-1 curcumin group were significantly increased(P<0.01),and the expression levels of Bcl-2 protein was significantly decreased(P<0.05 or P<0.01);compared with LNCaP group,the expression levels of Bax,cleaved Caspase-3,and PARP1 proteins in the cells in LNCaP+20 μmol·L-1 curcumin group and LNCaP+40 μmol·L-1 curcumin group were significantly increased(P<0.01),and the expression level of Bcl-2 protein in the cells in LNCaP+40 μmol·L-1 curcumin group was decreased(P<0.01);compared with shNC-C4-2 group,the expression levels of Bax,cleaved Caspase-3,and PARP1 proteins in the cells in shNC-C4-2+20 μmol·L-1 curcumin group were significantly increased(P<0.05 or P<0.01),and the expression level of Bcl-2 protein was significantly decreased(P<0.05);compared with shNC-C4-2+20 μmol·L-1 curcumin group,the expression levels of Bax and cleaved Caspase-3 proteins in the cells in shCD147-C4-2+20 μmol·L-1 curcumin group were significantly decreased(P<0.01);compared with shNC-LNCaP group,the expression levels of Bax,cleaved Caspase-3,and PARP1 proteins in the cells in shNC-LNCaP+20 μmol·L-1 curcumin group were significantly increased(P<0.05 or P<0.01),and the expression level of Bcl-2 protein was significantly decreased(P<0.05);compared with shNC-LNCaP+20 μmol·L-1 curcumin group,the expression levels of Bax,cleaved Caspase-3,and PARP1 proteins in the cells in shCD147-LNCaP+20 μmol·L-1 curcumin group were significantly decreased(P<0.05 or P<0.01),and the expression level of Bcl-2 protein was significantly increased(P<0.05).Compared with C4-2 group,the expression levels of E-cadherin protein in the cells in C4-2+20 μmol·L-1 curcumin group and C4-2+40 μ mol·L-1 curcumin group were significantly increased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins were significantly decreased(P<0.01);compared with LNCaP group,the expression levels of E-cadherin protein in the cells in LNCaP+20 μmol·L-1 curcumin group and LNCaP+40 μmol·L-1 curcumin group were significantly increased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins in the cells in LNCaP+40 μmol·L-1 curcumin group were significantly decreased(P<0.01);compared with shNC-C4-2 group,the expression levels of N-cadherin and Vimentin proteins in the cells in shNC-C4-2+20 μmol·L-1 curcumin group were significantly decreased(P<0.01);compared with shNC-C4-2+20 μmol·L-1 curcumin group,the expression level of E-cadherin protein in the cells in shCD147-C4-2+20 μmol·L-1 curcumin group was significantly decreased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins were significantly increased(P<0.01);compared with shNC-LNCaP group,the expression level of E-cadherin protein in the cells in shNC-LNCaP+20 μmol·L-1 curcumin group was significantly increased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins were significantly decreased(P<0.01);compared with shNC-LNCaP+20 μmol·L-1 curcumin group,the expression level of E-cadherin protein in the cells in shCD147-LNCaP+20 μmol·L-1 curcumin group was significantly decreased(P<0.01),and the expression level of N-cadherin was significantly increased(P<0.05).Conclusion:Curcumin inhibits the proliferation,migration,and invasion of the prostate cancer cells in vitro and induces the apoptosis;silencing the CD147 gene partially reduces its inhibitory effect and its ability to induce the apoptosis.

In-stent restenosis(ISR)and in-stent thrombosis(IST)are two major complications of percutaneous coronary in-tervention(PCI)and are also the main limiting factors in the treatment of obstructive coronary artery disease.In-stent neoathero-sclerosis(ISNA)serves as the common pathological basis for ISR and IST.Current research on ISNA is mainly based on clinical imaging observations using optical coherence tomography(OCT),angioscopy,intra vascular ultrasonography(IVUS),and autop-sy reports.The specific mechanisms and treatment strategies for ISNA are not clear yet.A comprehensive understanding of the epidemiological characteristics,histological features,and pathogenic mechanisms of ISNA not only helps in the prevention and treatment of post-stent complications,but also lays the foundation for the development of the next generation of coronary stents.This review summarizes the research progress on the development history of ISNA,the pathological features of ISNA,and the pathogenic mechanisms of ISNA.