Objective:To optimize the formulation of HA-CA liposomes and to study the anti-tumor effect of HA-CA liposomes on uterine cervical carcinoma mice.Methods:The methods of preparing HA-CA liposomes were screened,and the optimal fomulation was selected by the orthogonal design experiment with the the phospholipids/cholesterol ratio,the drug/lipids ratio and the pH value of PBS buffer was 7.4 as entrapment enfficiency was the index.The release of HA-CA liposomes was studyed by dialysis bag method.Uterine cervical carcinoma cells were inoculated subcutaneously into right axillary ofBal b/c mice,after continuous treatment of 14 d,we weighed the tumor and calculated the rate of tumor growth inhibition.Results:HA-CA liposomes were prepared by thin film hydration methods.The optimal parameters were as follows:the phospholipids/cholesterol ratio was 4∶1,the drug/lipids ratio was 1∶ 30,the pH value of PBS buffer was 7.4.The release curve of HA-CA liposome and CA liposome was basically the same,both of which a sustained-release efficacy.The cumulative release of HA-CA liposomes and CA liposomes were 78.39％ and 83.01％ at 48h.The inhibition rate of HA-CA liposomes on U14 cervical cancer mice was 60.39％ and significantly higher than that of positive control group,which was higher than that of CA and CA liposomes.Conclusions:HA-CA liposomes can significantly inhibit the effect of U14 cervical cancer nude mice higher than that of CA and CA liposomes owe to the modification of the active target ligand HA.

This article reviews the training model of orthopedic residents in the world's top orthopedic hospitals, such as Hospital for Special Surgery Affiliated to Cornell University and The Affiliated Hospital of Harvard University Medical School, and it is found that there are differences between China and the US in the training of orthopedic residents in the aspects of the admittance system of physicians, the setting of training contents , and the training model of orthopedic residents . The training of orthopedic residents in the US adheres to the concept of elite education and pays attention to the construction of tutors and learning atmosphere. The enlightenment to the training of orthopedic residents in China includes further clarification of the training objectives of orthopedic residents , improvement of the stage-based training system , integration of excellent medical teaching resources , and improvement of teaching methods and assessment systems.

Objective According investigate the expression of NLRP3 in liver tissues of mice with hepatic ischemia-reperfusion injury (HIRI),to determin the role of NLRP3 in the process of HIRI.Methods Established mice model of partial HIRI.Forty-two male C57BL/6 mice (aged 7 to 8 weeks,weight 20 to 25 g) were respectively divided into 7 groups:no-treatment control group,sham operation group,HIRI groups (2、6、12、24 h) and CY-09 group,6 mice in each group.The injury of the hepatic tissues in the 7 groups was analyzed based on detecting the levels of alanine transaminase (ALT),aspartate transaminase (AST),interleukin-1β (IL-1β),interleukin-18 (IL-18),tumor necrosis factor-α (TNF-α) by ELISA.HE and TUNEL staining were used to observe the pathological changes of liver tissues after HIRI.Western blotting assay were carried out to detect the expressions of NLRP3 and Caspase-1.Measurement data were expressed as mean ± standard deviation (Mean ± SD),and one-way variance analysis was used for comparison between groups.If the variance was not uniform,Dunnett C test was used.Results Serum ALT,AST,IL-1 β,IL-18 and TNF-α of mice detected in HIRI groups were higher than no-treatment control group and sham operation group at all endpoints (P ＜ 0.05).The relative expression of NLRP3 and Caspase-1 in the liver tissues of mice in the HIRI groups were significantly higher than that in the no-treatment control group and sham operation group.Serum ALT,AST,IL-1β,IL-18 and TNF-α of mice detected in CY-09 group were lower than HIRI groups at all endpoints (P ＜ 0.05).Less hepatocellular necrosis were exhibited in CY-09 group,comparing to HIRI groups.The hepatocyte apoptosis rate of mice in the CY-09 group was significantly lower than that in the 12 h HIRI group (P ＜ 0.05).The relative expression of NLRP3 in the liver tissues of mice in the CY-09 group was significantly lower than that in other groups.The relative expression of Caspase-1 in the liver tissues of mice in the CY-09 group was significantly lower than that in other groups except the no-treatment control group and sham operation group.Conclusions HIRI cause an increase in NLRP3 expression.The inhibition of NLRP3 can reduce HIRI.

The dose-related adverse effects of MDM2‒P53 inhibitors have caused significant concern in the development of clinical safe anticancer agents. Herein we report an unprecedented homo-PROTAC strategy for more effective disruption of MDM2‒P53 interaction. The design concept is inspired by the capacity of sub-stoichiometric catalytic PROTACs enabling to degrade an unwanted protein and the dual functions of MDM2 as an E3 ubiquitin ligase and a binding protein with tumor suppressor P53. The new homo-PROTACs are designed to induce self-degradation of MDM2. The results of the investigation have shown that PROTAC

Objective To investigate the therapeutic effect of Shugan Heluo Xingpi Decoction on CCl 4 -induced liver fibrosis in rats, and the underlying molecular mechanism. Methods Sixty male SPF Wistar rats were randomly assigned to six groups: blank control, model, positive control, high, medium or low dose groups of Shugan Heluo Xingpi Decoction ( n =10 per group). The liver fibrosis rat model was induced by an intraperitoneal injection of 40% CCl 4 oil solution. Rats in the blank control and model groups were administered 10 mL/kg normal saline by gavage, rats in the positive control group were administered 50 mg/kg silibinin meglumine by gavage, while rats in high-dose, medium-dose and low-dose groups of Shugan Heluo Xingpi Decoction were administered 12.42 g/kg, 6.21 g/kg and 3.11 g/kg (crude drug/body weight) by gavage, respectively, daily for 8 weeks. Rats was sacrificed after 8 weeks, during which the physiological status of rats in each group was dynamically monitored. Following sacrifice, serum was collected to detect HYP using alkaline hydrolysis colorimetry and the expression levels of AST, ALT, total protein (TP), and Alb using an automatic biochemical analyzer. The pathological morphological changes in the liver were detected by H & E staining and Masson staining, and the mRNA and protein levels of Wnt1, β-Catenin and Cyclin D1 were detected by RT-qPCR and Western Blot. Measurement data were compared across groups using one-way ANOVA with post-hoc LSD- t test. Results Compared with the model group, after silibinin meglumine and Shugan Heluo Xingpi Decoction intervention, the physiological status of rats was significantly improved; serum levels of HYP, ALT, AST and Glo were significantly decreased, while serum levels of TP, Alb and A/G were significantly increased (all P < 0.05). Compared with the positive control group, serum levels of ALT and AST were significantly increased (all P < 0.05), while the levels of TP, Alb and A/G were significantly decreased (all P < 0.05) in low-dose group of Shugan Heluo Xingpi Decoction. H&E staining showed mild portal vein fibrosis with a few fibrous septa and mild steatosis of hepatocytes in the positive control group, obvious portal vein fibrosis with a few fiber septum in the low dose group, a few portal vein fibrosis in the medium dose group, while no obvious abnormality in the high dose group of Shugan Heluo Xingpi Decoction. Masson staining revealed that the therapeutic effect of high dose group of Shugan Heluo Xingpi Decoction on collagen deposition was superior to silibinin meglumine and medium and low dose of Shugan Heluo Xingpi Decoction (all P < 0.05), and was generally equivalent to high dose of Shugan Heluo Xingpi Decoction. Silibinin meglumine and medium and high doses of Shugan Heluo Xingpi Decoction inhibited more significantly the mRNA and protein expression of Wnt1, β-catenin and Cyclin D1 (all P < 0.05). Conclusion Shugan Heluo Xingpi Decoction shows anti-hepatic fibrosis effect, with a greater effect at higher doses. Regulating Wnt/β-Catenin signaling pathway may be one of the underlying molecular mechanisms.

  Objective  To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome.  Methods  Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected.  Results  The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate.  Conclusions  The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.