OBJECTIVETo explore the inflammatory cascade mechanism through Toll like receptor 2 (TLR2) pathway after cerebral ischemia/reperfusion, and to study molecular mechanisms of Guanmaitong (GMT) Tablet for protecting brain damage.

METHODSWe used bolt-line method to block/release the middle cerebral artery, causing cerebral ischemia/reperfusion (I/R) injury model. GMT Tablet was given by gastrogavage. Rats were then divided into the high dose GMT group (1200 mg/kg), the middle dose GMT group (600 mg/kg), the low dose GMT group (300 mg/kg), the positive control group (Tanakan, 20 mg/kg). Their right brain tissues were fixed in 10% neutral formalin. TLR2 expressions were detected by immunofluorescence staining. The total protein was extracted from right brain tissues by ultrasonica- tion. Expression levels of extracellular regulated protein kinases (ERK), phospho-extracellular regulated protein kinases (p-ERK), p38-mitogen activated protein kinases (p-ERK), phospho-p38-mitogen activated protein kinases [p-p38-MAPKs(p-p38)] were assessed by Western blot. Abdominal aortic blood was withdrawn. IL-6 and IL-1β levels were detected by ELISA in brain tissues and serum.

RESULTSCompared with the sham-oepration group, expression levels of TLR2, ERK, p-ERK, p38, p-p38 protein were up-regulated (P < 0.05, P < 0.01), and contents of IL-6 and IL-1β in brain tissues and serum were increased in the model group (P < 0.01). Expression levels of TLR2, ERK, p-ERK, p38, p-p38 were down-regulated (P < 0.05, P < 0.01), and contents of IL-6 and IL-1β were reduced in brain tissues and serum in middle and high dose GMT groups (P < 0.05, P < 0.01).

CONCLUSIONSTLR2 pathway was involved in cerebral I/R injury. GMT protected neurons by down-regulating protein expressions of TLR2, ERK, p-ERK, p38, p-p38 and contents of IL-1β and IL-6.

Animals ; Blotting, Western ; Brain Ischemia ; metabolism ; Cerebral Infarction ; Down-Regulation ; Drugs, Chinese Herbal ; therapeutic use ; Interleukin-1beta ; Interleukin-6 ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; Tablets ; Toll-Like Receptor 2 ; metabolism ; Up-Regulation ; p38 Mitogen-Activated Protein Kinases ; metabolism

AIMTo explore the feasibility and safety of greenlight photoselective vaporization of the prostate (PVP) on high-risk patients presenting with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH) and to evaluate their clinical and voiding outcome.

METHODSA total of 85 high-risk patients with obstructive BPH underwent PVP with an 80 W potassium-titanyl-phosphate laser, which was delivered through a side-deflecting fiber with a 23 Fr continuous flow cystoscope. Operative time, blood loss, indwelling catheterzation, international prostate symptom score (IPSS), quality of life score (QoL), uroflowmetry, postvoid residual urine volume and short-term complication rates were evaluated for all patients.

RESULTSAll patients got through the perioperative period safely. The chief advantages of PVP were: short operative time (25.6 +/- 7.6 min), little bleeding loss (56.8 +/- 14.3 mL) and short indwelling catheterization (1.6 +/- 0.8 d). The IPSS and QoL decreased from (29.6 +/- 5.4) and (5.4 +/- 0.6) to (9.5 +/- 2.6) and (1.3 +/- 0.6), respectively. The vast majority of patients were satisfied with voiding outcome. The mean maximal urinary flow rate increased to 17.8 mL/s and postvoid residual urine volume decreased to 55.6 mL. These results are significantly different from preoperative data (P < 0.05). No patient required blood transfusion or fluid absorption. There were few complications and very high patient satisfaction after operation.

CONCLUSIONPVP has a short operative time and high tolerance, and is safe, effective and minimally invasive for high-risk patients, therefore it might be considered as a good alternative treatment for high-risk patients with obstructive urinary symptoms as a result of BPH.

Aged ; Aged, 80 and over ; Humans ; Laser Therapy ; adverse effects ; Male ; Phosphates ; Prospective Studies ; Prostatic Hyperplasia ; surgery ; Titanium ; Treatment Outcome ; Urination Disorders ; epidemiology

OBJECTIVETo investigate the feasibility and safety of adult-to-adult living-related donor liver transplantation using a right lobe graft.

METHODSThe clinical data of 2 cases of living-related donor liver transplantation performed between July, 2010 and November, 2010 were analyzed.

RESULTSLiver transplantation was performed using a right lobe graft including the middle hepatic vein in one case and a right lobe graft without the middle hepatic vein in the other. The ratio of graft volume to standard liver volume was 46.2% and 47.3% in the two cases, with GR/WR of 0.83 and 0.80, and donor residue liver of 42.1% and 39.5%, respectively. The donor operation lasted for 6.5 h and 5 h in the two cases with blood loss of about 200-250 ml without blood transfusion. The donors recovered uneventfully without any surgical complications, whose liver function was normal 7 days after the operation, and were discharged 14 days and 16 days after the surgery, respectively. The recipient operation lasted for 8 h and 7 h with blood loss of about 800-1000 ml. The right hepatic vein, hepatic artery, portal vein and bile duct reconstruction were performed by end-to-end anastomoses in the 2 recipients. Bile duct anastomosis stricture occurred in the first recipient 2 months after transplantation and was treated with percutaneous transhepatic cholangiography and drainage. The second recipient recovered smoothly without any complications. The recipients have so far survived 9 months and 5 months, respectively.

CONCLUSIONAdult-to-adult living-related donor liver transplantation is a safe and effective option for treatment of end-stage liver diseases in the context of cadaveric liver graft shortage.

Adult ; Female ; Hepatectomy ; Humans ; Liver Cirrhosis ; surgery ; Liver Neoplasms ; surgery ; Liver Transplantation ; methods ; Living Donors ; Male ; Middle Aged ; Retrospective Studies

BACKGROUNDNuclear mitotic apparatus protein 1 (NuMA1) had been reported to produce three groups of isoforms categorized as long, middle, and short groups, of which short NuMA displayed distinct localization patterns compared to long and middle isoforms. However, the function of short NuMA was not clear in the progress of cancer formation. This study aimed to unveil the role of short NuMA in cancer pathogenesis.

METHODSThe expression levels of short isoforms were explored in paired gastric carcinoma (GC) samples and different cell lines. Furthermore, the short isoform behaved as a putative tumor suppressor based on cell proliferation and cell colony formation assays. Pull-down assay and whole-genome gene expression analysis were carried out to search candidate interaction partners of short NuMA.

RESULTSThe expression of short NuMA was highly expressed in S and G2 phases of the cell cycle; compared with nontumor tissues, short NuMA downregulated in nine GCs (GC1 [0.131, P = 5 × 10-4]; GC2 [0.316, P = 3 × 10-5]; GC3 [0.111, P = 6 × 10-4]; GC4 [0.456, P = 0.011]; GC5 [0.474, P = 0.001]; GC6 [0.311, P = 0.004]; GC7 [0.28, P = 3 × 10-5]; GC8 [0.298, P = 0.007]; and GC9 [0.344, P = 0.002]). Besides, high expression of short NuMA significantly inhibits cell growth (2.43 × 105 vs. 2.97 × 105, P = 0.0029) and cell clone information in vitro (70 vs. 2, P = 1.67 × 10-45). Short NuMA could bind with alpha-actinin-4 (ACTN4), a putative tumor promoting gene. Overexpression of short NuMA could tremendously decrease the expression of MYB proto-oncogene like 2 (MYBL2) of about 92-fold, which played an important role in the cell cycles.

CONCLUSIONSShort isoform of NuMA might be functioned as a putative role of tumor suppressor. Further studies should be made to illuminate the relationship between ACTN4, MYBL2, and tumor progression.

The 2-(2-phenylethyl)chromones were separated from agarwood of Aquilaria agallocha Roxb. and their anti-KRAS mutant non-small cell lung cancer (NSCLC) activities were evaluated. 2-(2-Phenyethyl)chromones in agarwood were separated and purified by silica gel, RP-18 reverse phase silica gel, MCI gel CH20P, Diol, and semi preparative HPLC chromatography techniques, while the structures of the compounds were identified by extensive spectroscopic analysis, such as 1D and 2D NMR and ESI-MS. The cell counting kit 8 (CCK-8) assay was used to screen the anti-tumor activity of the isolated monomeric compounds on three KRAS-mutant NSCLC cells. The cell proliferation, cloning formation, adhesion ability, and cell cycle arrest activity of compound 8 were analyzed. Molecular docking and Western blot experiments were used to study the mechanism of compound 8. The in vivo anti-tumor activity of the compound 8 was evaluated by zebrafish cell derived xenograft (CDX) model. Nineteen known 2-(2-phenylethyl)chromones were isolated from the ethyl acetate extract of agarwood. On A549 (KRAS G12S) cells, compounds 8, 10, and 19 showed good inhibitory activity, on H23 (KRAS G12C) cells, compounds 7, 8, and 19 showed good inhibitory activity, and on H358 (KRAS G12C) cells, compounds 8, 10, and 16 showed good inhibitory activity. Compound 8 had the best inhibitory activity in all three cell lines. It effectively inhibited cell proliferation, clone formation, adhesion ability, and arrested the H23 cell cycle at G2/M phase. Compound 8 could also inhibit the expression of c-Met and its downstream signaling pathways, effectively inhibiting tumor growth in zebrafish CDX model. In conclusion, among the nineteen known 2-(2-phenylethyl)chromones, compound 8 had the best activity and significantly inhibited the proliferation of KRAS-mutant NSCLC cells by arresting the cells in the G2/M phase.