Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

Objective To investigate the effect of Yangxue Rougan pills on a rat model of liver fibrosis induced by multiple factors and the mechanism of action of Yangxue Rougan pills in the treatment of liver fibrosis. Methods A total of 50 male rats were randomly divided into blank control group, multi-factor model group, Fuzheng Huayu capsule group, and high-, middle-, and low-dose Yangxue Rougan pill groups. The rats in the blank control group were given normal water and feed, and those in the other groups were given modified high-fat low-protein diet and 5% alcohol, as well as subcutaneous injection of olive oil solution containing 40% carbon tetrachloride and intraperitoneal injection of pig serum 0.5 mL per rat, twice a week for 12 consecutive weeks. Since week 7, the rats in the high-, middle-, and low-dose Yangxue Rougan pill groups were given Yangxue Rougan pills at a dose of 9.5, 4.75, and 2.38 g/kg, respectively, those in the Fuzheng Huayu capsule group were given Fuzheng Huayu capsules at a dose of 0.75 g/kg, and those in the blank control group and the multi-factor model group were given an equal volume of distilled water by gavage every day for 6 consecutive weeks. The rats were treated at week 12. HE staining and Masson staining were used to observe the degree of liver fibrosis in rats, and PCR and Western blot were used to measure the expression of TGF-β1, Smad3, and Smad7 in the liver. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the Dunnett's t -test was used for further comparison between two groups. Results Compared with the blank control group, the multi-factor model group had a severely damaged lobular structure and a significantly higher degree of liver fibrosis, with the formation of pseudolobules with different sizes; compared with the multi-factor model group, the Yangxue Rougan pill groups had a significant improvement in the degree of liver fibrosis, with the most significant therapeutic effect in the high- and middle-dose Yangxue Rougan pill groups. Compared with the blank control group, the multi-factor model group had significant increases in the expression of TGF-β1 and Smad3 and a significant reduction in the expression of Smad7 in liver tissue (all P < 0.05); compared with the multi-factor model group, the Yangxue Rougan pill groups had a significant reduction in the expression of TGF-β1 and a significant increase in the expression of Smad7 (all P < 0.05); compared with the multi-factor model group, the high- and middle-dose Yangxue Rougan pill groups had a significant reduction in the expression of Smad3 (both P < 0.05). Conclusion Yangxue Rougan pills can significantly inhibit liver fibrosis in rats by downregulating the expression of TGF-β1 and Smad3 and upregulating the expression of Smad7, and therefore, the TGF-β1/Smad signaling pathway is one of the mechanisms of action of Yangxue Rougan pills in improving liver fibrosis.

Maintenance hemodialysis can improve many symptoms of patients with end-stage renal disease, but long-term dialysis can cause various physiological symptoms and psychological negative emotions. As a positive psychological change, post-traumatic growth plays a role in relieving patients' psychological pressure and reducing their pain. However, the post-traumatic growth of patients with maintenance hemodialysis needs to be improved. This article reviewed the status, influencing factors and interventions of post-traumatic growth in maintenance hemodialysis patients in order to provide reference for psychological care of such patients.

Shengmai Yin (SMY) is a Chinese herbal decoction that effectively alleviates the side effects of radio-therapy in various cancers and helps achieve radiotherapy's clinical efficacy.In this study,we explored the interaction mechanism among SMY,DNA methylation,and nasopharyngeal carcinoma (NPC).We identified differences in DNA methylation levels in NPC CNE-2 cells and its radioresistant cells (CNE-2R)using the methylated DNA immunoprecipitation array and found that CNE-2R cells showed genome-wide changes in methylation status towards a state of hypomethylation.SMY may restore its original DNA methylation status,and thus,enhance radiosensitivity.Furthermore,we confirmed that the dif-ferential gene Tenascin-C (TNC) was overexpressed in CNE-2R cells and that SMY downregulated TNC expression.This downregulation of TNC inhibited NPC cell radiation resistance,migration,and invasion.Furthermore,we found that TNC was hypomethylated in CNE-2R cells and partially restored to a hypermethylated state after SMY intervention.DNA methyltransferases 3a may be the key protein in DNA methylation of TNC.

Aim To investigate the effect of curcumin on radiosensitivity of radioresistant nasopharyngeal carcinoma cell line CNE-2R and its mechanism.Methods The concentration of curcumin was screened by MTT assay.Dose-survival curves were obtained according to the colony forming test for L-Q matching and multitarget-single hitting matching,while SF2 and the correlation parameters of radiation biology were calculated.The changes of cell cycle in CNE-2R cells caused by curcumin were also tested by flow cytometry(FCM).The differential expression of genes related to cell cycle and DNA damage repair were detected by RT-qPCR.Results CNE-2R cells could not be inhibited by 10 μmol·L-1 curcumin.Dealt with 10 μmol·L-1 curcumin for 24 h,the value of α/β increased to 1 596 from 6.56;the value of SF2 decreased to 0.361 Gy from 1.93 Gy;the value of N decreased to 1.06 from 1.60;the value of D0 decreased to 2.12 from 3.27;the value of Dq decreased to 0.12 from 1.53.FCM showed that the cells in G2 phase had a significant increase and the cells in S phase had a significant decrease after dealt with 10 μmol·L-1 curcumin for 24 h.The expression of CDK4 was significantly up-regulated and GADD45g,BRCA1 were significantly down-regulated.Conclusion Curcumin radiosensitizes nasopharyngeal carcinoma cell line CNE-2R by changing cell cycle and affecting DNA damage repair through regulating the expression of CDK4,GADD45 g and BRCA1.

Objective To study the effects of ginkgo biloba extract(GBE)on c-reactive protein(CRP) and tumor necrosis factor-α(TNF-α)in serum and alveolar lavage fluid(BALF)from rats with chronic obstructive pulmonary disease(COPD). Methods 90 rats were randomly divided into groups A,B,C,D,E and F. There were 15 rats in each group. The rat model of COPD were established in groups B,C,D,E and F. Groups C and D were given intraperitoneal injections with GBE from day l to day l4 and day 29 to day 42. Groups E and F weregiven intraperitoneal injections with erythromycin from day l to day l4 and day 29 to day 42. After the end of experi-ment ,the contents of CRP and TNF-α in serum and BALF were detected in all groups. Results The contents of CRP and TNF-α in the serum and the BALF were markedly lower in groups C,D,E and F than in group B (P<0.05);and the contents of CRP in the serum and the BALF and TNF-αin the BALF were lower in groups C, E and F than in group D(P<0.05). Conclusions GBE can inhibit the airway and systemic inflammatory response in COPD rats. Early intervention is more effective.

Objective To investigate the effect of up-regulation of miR-132 on expressions of angiopoietin-1 (Ang-1)/endothelium-specific tyrosine kinase receptor 2 (Tie2) in focal cerebral ischemia reperfusion injury of rats.Methods Forty adult healthy SD rats were randomly divided into sham-operated group,cerebral ischemia group,miR-132 mimic group and negative control group (n=10).The models of middle cerebral artery occlusion in the later three groups were established by using modified Longa suture method.Rats in the miR-132 mimic group and negative control group were injected miR-132 mimic 15 μg and negative control 15 μg via paracele.Rats in each group were sacrificed 24 h after ischemia,and the brain tissues were collected;the total infarct volumes were calculated by TTC staining.The mRNA expressions ofmiR-132,Ang-1 and Tie2 in ischemic cerebral cortex tissues were detected by real-time fluorescence quantitative PCR.The protein expressions of Ang-1,Tie2,CD31 and vessel endothelial growth factor (VEGF) in ischemic cerebral cortex tissues were detected by Western blotting.Results The total infarct volume in the miR-132 mimic group was (27.92±3.05) mm3,which was significantly smaller than that in the cerebral ischemia group and negative control group ([51.34±2.86] mm3 and [50.46±2.57] mm3,P＜0.05).The relative mRNA expression levels of miR-132,A ng-1,Tie2,and the protein expression levels of Ang-1,Tie2,CD31,VEGF in the ischemic cerebral cortex tissues of the miR-132 mimic group were significantly higher than those in the negative control group,cerebral ischemia group and sham-operated group (P＜0.05);and those in the negative control group and cerebral ischemia group were significantly higher than those in the sham-operated group (P＜0.05).Conclusion Up-regulation ofmiR-132 expression could improve the ischemic states of ischemic stroke in rats,which might be related to Ang-1/Tie2 increased expressions to promote angiogenesis in ischemic brain tissues.

Objective To compare the effects of adjustable pressure drainage device, negative pressure ball drainage and drainage bag drainage on patients with the total hip arthroplasty. Methods The silicone drainage ball with negative pressure, the urine collection bag, the infusion set′s regulator were used to make adjustable pressure drainage device. 120 cases of total hip arthroplasties from January to December in 2015 were chosed and divided randomly into 3 groups based on the sequence of operation notifications. In 40 cases, drainage bag were used (control group 1), 40 cases with negative pressure ball drainage (control group 2) and 40 cases with adjustable pressure drainage device (experimental group). Total postoperative bleeding, the blood transfusion amount, swelling (the thickness of hematoma) and the nursing workload of the three groups were compared. Results The total postoperative bleeding, the blood transfusion amount, the thickness of hematoma and the nursing workload in the experimental group were (775.1±130.5) ml, (3.5±1.3) mm, (180.2±29.9) ml, (34.5±5.2) min. The total postoperative bleeding, the blood transfusion amount, the thickness of hematoma and the nursing workload in the control group 1 were (889.4 ± 160.8) ml, (5.2 ± 1.1) mm, (285.9 ± 30.4) ml, (40.6 ± 7.4) min and in the control group 2 were (876.2±156.7) ml, (4.3±1.2) mm,(208.3±33.3) ml, (50.3±8.5) min. Compared the data of the experimental group and the control group 1, the difference was of statistically significance (t=3.49-15.68, P < 0.01). Compared the data of the experimental group and the control group 2, the difference was of statistically significance (t=2.86-10.03, P<0.01). Conclusions The effects of adjustable pressure drainage device are better than the drainage bag and negative pressure drainage ball. It can effectively reduce the postoperative bleeding and the swelling degree, and bring a lot of relief to the patients and lots of convenience to the nursing work. The method is affordable, reliable and safe which should be promoted in the primary hospital.

Objective To investigate the values of conventional magnetic resonance imaging (MRI),magnetic resonance angiography (MRA),and high-resolution MRI for diagnosing intracranial arterial dissection (IAD)caused ischemic stroke. Methods From August 2008 to April 2015,59 consecu-tive patients (age 45 ±15years,41males)with IAD caused ischemic stroke admitted to the First Affiliated Hos-pital of Sun Yat-Sen University were enrolled prospectively. All patients underwent conventional cranial MRI/MRA examination,25 of them underwent whole brain DSA examination,and 10 underwent high-resolution MRI. The findings of conventional MRI/ MRA and high-resolution MRI of IAD were analyzed. For patients undergoing DSA,the proportions of detection and compliance of IAD were compared between DSA and conventional MRI / MRA. Results (1)Conventional MRI / MRA revealed typical sign of artery dissection in 42 patients (71. 2%),among them,the intramural hematoma (n = 22,52. 4%)was most common. Other common signs included intimal flap/ double lumen sign (n = 13,31. 0%)and long irregular or thread-like stenosis (n = 9,21. 4%);while dissecting aneurysm (n = 7,16. 7%)and rat tail-shaped occlusion (n = 3, 7. 1%)were relatively rare. In 17 patients (28. 8%)with IAD that conventional MRI/ MRA did not detect the typical dissection sign,the dissections were involved in the middle cerebral artery (11 / 17,64. 7%), they were more common than the 42 patients with IAD (10 / 42,23. 8%)detected the typical dissection sign by conventional MRI/ MRA. There was significant difference (P = 0. 006). (2)Among the 25 patients undergoing DSA,DSA revealed that 15 patients (60%)had the typical dissection sign,and conventional MRI/ MRA only revealed 8 of them (32%)with the typical dissection sign,but there was no significant difference (P = 0. 088). In 15 patients with IAD that DSA detected the typical dissection sign;conventional MRI / MRA detected the typical dissection sign in 8 of them. The diagnostic coincidence rate was 8 / 15. (3)Both conventional MRI/ MRA and DSA revealed non-specific limitation stenosis or cut-off occlusion in 10 patients (16. 9%)with IAD,while the high-resolution MRI revealed intimal flap in 5 of them,intramural hematoma in 4,and intimal flap and intramural hematoma in 1. Conclusion Conventional cranial MRI/MRA is an effective technique for revealing IAD,whereas high-resolution MRI has the unique advantages for diagnosing IAD without typical dissection in other vascular imaging.

Objective To establish an HPLC method for the simultaneous determination of the 6 aconitum alkaloids in compoundTengwu Ointment.Methods Chromatographic column was Aglient XDB-C18 column (4.6 mm × 250 mm, 5μm), with the mobile phase A of acetonitrile- tetrahydrofuran (25∶8), phase B was 0.1 mol/L ammonium acetate solution (0.5 mL acetic acid added to the 1000 mL) with gradient elution;the flow rate was 1 mL/min;the detection wavelength was set at 235 nm;the column temperature was 25℃.Results Aconitine was in the good linear range of 0.072-0.648μg (r=0.999 5), with the average recovery of 99.29%, RSD=1.25%. Mesaconitine was in the good linear range of 0.062-0.648μg (r=0.999 5), with the average recovery of 99.12%, RSD=0.85%. Hypaconitine was in the good linear range of 0.064-0.384μg (r=0.999 8), with the average recovery of 99.57%, RSD=1.07%. Benzoylaconine was in the good linear range of 0.056-0.672μg (r=0.999 2), with the average recovery of 98.11%, RSD=0.61%. Benzoylmesaconine was in the good linear range of 0.055-0.993μg (r=0.999 9), with the average recovery of 99.27%, RSD=1.10%. Benzoylhypaconine was in the good linear range of 0.078-0.702μg (r=0.999 8), with the average recovery of 99.08%, RSD=1.38%.Conclusion This method is simple, sensitive, repeatable and accurate, which can be used for determination of aconitum alkaloids in compoundTengwu Ointment.