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.

BACKGROUNDUp to now, locally advanced non-small cell lung cancer simutaneously involving carina, heart and great vessels is still regarded as contraindication for surgical treatment. However, the prognosis is very poor in these patients treated with chemotherapy and/or chemoradiotherapy. The aim of this study is to summarize the clinical experiences of carinoplasty combined with heart and great vessel plasty in the treatment of 84 patients with locally advanced non-small cell lung cancer involving carina, heart and great vessels or both in our hospital.

METHODSFrom March, 1988 to December, 2004, carinal resection and reconstruction combined with heart, great vessel plasty was performed in 84 patients with locally advanced non-small cell lung cancer involving carina, heart and great vessels simutaneously. The operative procedures in this series included as follows: (1) Right upper sleeve lobectomy combined with carinal resection and reconstruction, and right pulmonary artery sleeve angioplasty in 9 patients; (2) Right sleeve pneumonectomy combined with partial resection and reconstruction of left atrium, and superior vena cava resection and Gortex grafts in 3 cases; (3) Left upper sleeve lobectomy combined with carinoplasty, left pulmonary artery sleeve angioplasty and partial resection and reconstruction of left atrium in 3 cases; (4) Right upper sleeve lobectomy combined with carinoplasty, right pulmonary artery sleeve angioplasty and partial resection and reconstruction of left atrium in 10 cases; (5) Left upper sleeve lobectomy combined with carinoplasty and left pulmonary artery angioplasty in 9 cases; (6) Left upper sleeve lobectomy combined with carinoplasty, left pulmonary artery sleeve angioplasty and resection of the aorta arch sheath in 6 cases; (7) Right upper-middle sleeve lobectomy combined with carinoplasty and right pulmonary artery sleeve angioplasty in 3 cases; (8) Left upper sleeve lobectomy combined with carinoplasty, left pulmonary artery angioplasty, resection of the aorta arch sheath and partial resection and reconstruction of left artium in 8 cases; (9) Right upper sleeve lobectomy combined with carinoplasty, right pulmonary artery angioplasty and partial resection and reconstruction of left atrium in 4 cases; (10) Left sleeve pneumonectomy combined with partial resection and reconstruction of left atrium in 3 cases; (11) Right upper-middle sleeve lobectomy combined with carinoplasty, right pulmonary artery angioplasty and superior vena cava resection and reconstruction with Gortex grafts in 23 casese; (12) Right sleeve pneumonectomy combined with partial resection and reconstruction of left atrium in 1 case; (13) Right upper-middle sleeve lobectomy combined with carinoplasty, right pulmonary artery angioplasty and partial resection and reconstruction of left atrium in 1 case; (14) Right upper-middle sleeve lobectomy combined with carinoplasty, right pulmonary artery angioplasty and right inferior pulmonary vein sleeve resection and reconstruction in 1 case.

RESULTSThere were two operative death in this series. The operative mordality was 2.38%. A total of 32 patients had operative complications. The incidence of operative complications was 38.10%. The 1-, 3-, 5-and 10-year survival rate was 81.34%, 59.47%, 31.73% and 24.06% respectively.

CONCLUSIONS(1) It is feasible in technique that carinal resection and reconstruction combined with heart, great vessel plasty in the treatment of locally advanced non-small cell lung cancer involving carina, heart and great vessels simutaneously; (2) Multiple modality therapy based on carinal resection and reconstruction combined with heart and great vessel plasty can remarkably increase the survival rate, and improve the prognosis and quality of life in patients with locally advanced non-small cell lung cancer involving carina, heart and great vessels.

Objective:To study the effectiveness and safety of different acupuncture therapies in treating Posttraumatic stress disorder(PTSD)after Wenchuan‘5.12’earthquake.And choose a desirable acupuncture therapy.Methods:A total of 276 patients were recruited in this trial and randomly divided into four groups:scalp electric acupuncture group(group A),scalp electric acupuncture with moxibustion group(group B),scalp electric acupuncture with auricular acupuncture group(group C)and paroxetine hydrochloride group(group D).Each group was treated for 12 weeks.Patients were scored using Clinicianadministered Scale for DSM-IV(CAPS),Hamilton Depression Rating Scale for Depression(HAMD),and Hamilton Anxiety Scale(HAMA).Results:The study was finished well with a balanced grouping and fine baseline.After the analysis of integrations of CAPS,HAMD,and HAMA,we found that the score differences before and after the treatment were of statistical significance in all four groups(P

ObjectiveTo summarize the technique and preliminary outcome of Neuroform stent combined with Guglielmi detachable coil (GDC) to treat wide-necked intracranial aneurysms. Methods32 cases with aneurysms which underwent 32 endovascular procedures performed by using stent were retrospectively analyzed.The ratio of aneurysm neck/body is 1/2～1/1. Results24 aneurysms were completely occluded and other 8 were incompletely (>95%) occluded. Transient ischemia of cerebral occured in 2 cases. 14 aneurysms were followed up 0.5～1 year after. 2 aneurysms of them appeared neck remnant growth.ConclusionUsing Neuroform stent combined with GDC to treat wide-necked intracranial aneurysm may prevent the herniation of GDC into the artery and increase the outcome of wide-necked intacranial aneurysm.

In order to clarify the cellulose-utilizing mechanism of the Cerambycidae, the microorganism in the Apriona germari(Hope) larvae's gut was cultured and identified. A strain of facultative anaerobic cellulose-utilizing bacteria was isolated from the midgut fluid of A. germari larvae with the cellulose-congo red agar medium. The colonies of the bacteria were white and round with regular margin. Clear zones of cellulolysis surrounding the colonies might reach 10m～20mm. The size of the bacteria was 0.5μm～0. 8μm× l～3μm approximately. The cell was gram-positive rod with polar flagella. It hadn't spores. With the results of biochemical tests, the bacteria were tentatively identified as Cellulomonas.

In order to clarify the cellulose utilizing mechanism of the Cerambycidae, the microorganism in the Apriona germari(Hope) larvae’s gut was cultured and identified. A strain of facultative anaerobic cellulose utilizing bacteria was isolated from the midgut fluid of A. germari larvae with the cellulose congo red agar medium. The colonies of the bacteria were white and round with regular margin. Clear zones of cellulolysis surrounding the colonies might reach 10mm～20mm. The size of the bacteria was 0.5?m～0.8?m?1～3?m approximately. The cell was gram positive rod with polar flagella. It hadn't spores. With the results of biochemical tests, the bacteria were tentatively identified as Cellulomonas.