[The application and effect of bispherical augment in acetabular defects reconstruction].

Objective: To evaluate the clinical effect of bispherical augment in acetabular defects reconstruction in hip revision. Methods: This is a retrospective case series study. A retrospective analysis of 119 patients (124 hips) patients who underwent hip revision surgery and reconstructed with bispherical augment for acetabular bone defects from January 2019 to December 2023 was performed. There were 57 males (58 hips) and 62 females (66 hips), aged (65.0±11.8) years (range:40 to 102 years). The body mass index was (23.9±3.5) kg/m2 (range:16.1 to 32.2 kg/m2). Acetabular bone defects were typed as follows: 2 hips in Paprosky type ⅡA, 29 hips in type ⅡB, 34 hips in type ⅡC, 31 hips in type ⅢA, and 28 hips in type ⅢB, of which 9 patients (9 hips) were combined with pelvic discontinuity. Differences in Harris hip score (HHS) and lower limb discrepancy (LLD) were compared between preoperatively and final follow-up. The height of the hip center of rotation and the horizontal distance from the center of rotation to the teardrop were measured by radiographs before and after surgery, and prothesis stability and the occurrence of postoperative complications were evaluated. Data were compared using the paired sample t test. Results: All patients successfully completed the operation. The operation time was (167.0±53.4) minutes (range:90 to 380 minutes) and the intraoperative bleeding was (345.3±124.2) ml (range:100 to 1 200 ml). The height of the hip center of rotation decreased from (39.7±13.0) mm preoperatively to (21.8±7.1) mm postoperatively and the horizontal distance from the center of rotation to the teardrop increased from (34.0±10.1) mm preoperatively to (38.5±5.9) mm postoperatively, and the differences were statistically significant (t=15.859, P<0.01; t=5.266,P<0.01). All the patients were followed up for (26.1±15.4) months (range:6 to 60 months). At the last follow-up, HHS improved from (35.2±10.0) points preoperatively to (85.5±9.5) points, and the difference was statistically significant (t=50.723,P<0.01). LLD decreased from (2.1±1.1) cm preoperatively to (0.5±0.5) cm, and the difference was statistically significant (t=13.767, P<0.01). All acetabular components were stable and free of displacement on imaging during follow-up. Three patients suffered dislocation and received closed reduction, all prosthesis were in good position during follow-up. No dislocation, loosening, fracture, recurrence of infection and vascular nerve injury occurred in other patients. Conclusion: Bispherical augment can effectively reconstruct acetabular bone defects, restore the hip center of rotation, and improve hip joint function scores at short and mid-term follow-up.

Identification of ELAVL1 gene and miRNA-139-3p involved in the aggressiveness of NSCLC.

OBJECTIVE: Tumor metastasis remains the main cause for the cancer-associated death of human non-small-cell lung carcinoma (NSCLC). Many studies have verified that microRNAs (miRNAs) exert crucial functions in the development of NSCLC. Nevertheless, the functions of miR-139-3p in NSCLC remain unexplored. PATIENTS AND METHODS: The quantitative Real Time-PCR (qRT-PCR) assay was applied to assess the level of miR-139-3p and ELAV like RNA binding protein 1 (ELAVL1) in NSCLC tissues and cell lines. The growth of NSCLC cell was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and colony formation assay. The migration ability and invasiveness of NSCLC cells were analyzed using wound healing and transwell invasion analysis. The expression of ELAVL1 was determined by immunoblotting assay. The growth of NSCLC cell in vivo was assessed using xenograft model. RESULTS: We uncovered that miR-139-3p was down expressed in NSCLC. MiR-139-3p repressed NSCLC cell growth, migration as well as invasion in vitro, and suppressed the progression of NSCLC cell in vivo. Mechanistically, ELAVL1 was proved as a downstream target of miR-139-3p. The level of ELAVL1 was upregulated in NSCLC and inversely associated with miR-139-3p level. Immunoblotting assay suggested that ELAVL1 was negatively modulated by miR-139-3p in NSCLC cell. In vivo, miR-139-3p repressed NSCLC cell growth and metastasis. Several recuse assays revealed that ELAVL1 mediated the inhibitory actions of miR-139-3p on the growth and metastatic-related traits of NSCLC cell. CONCLUSIONS: Our results indicate that miR-139-3p acts as a suppressor in modulating the aggressiveness of NSCLC via regulating ELAVL1.

[Laparoscopic diagnosis of postoperative recurrence of peritoneal metastasis in gastric cancer patients and the clinical efficacy of bidirectional intraperitoneal and systemic chemotherapy].

Objective: To explore the diagnostic value of laparoscopy in the postoperative recurrence of peritoneal metastasis in gastric cancer, and to investigate the efficacy of bidirectional intraperitoneal and systemic (BIPS) chemotherapy for the recurrence. Methods: The descriptive case series study was conducted. Case inclusion criteria: (1) gastric cancer patients without synchronous distant metastasis received D2 radical gastrectomy; (2) postoperative adjuvant chemotherapy was administered; (3) no other distant metastasis except recurrence of peritoneal metastasis; (4) age of 18-75 years; (5) Eastern Cooperative Oncology Group (ECOG) performance-status score≤2; (6) pretreatment evaluation suggested that surgery and chemotherapy could be tolerated. Eight consecutive gastric cancer patients with postoperative recurrence of peritoneal metastasis who met the above criteria at Department of Gastrointestinal Surgery of Ruijin Hospital from September 2015 to September 2016 were enrolled into the study. There were 6 males and 2 females with the median age of 52 (38-68) years. They received laparoscopy or laparotomy first, and then were evaluated with reference to the Sugarbaker peritoneal cancer index (PCI) and the peritoneal metastasis classification of gastric cancer developed by the Japanese Gastric Cancer Research Association. A peritoneal access port was implanted in the subcutaneous space of the lower abdomen and the patients received chemotherapy for 21 days as a course of treatment. All the patients received intraperitoneal 20 mg/m(2) of paclitaxel (PTX) via implanted subcutaneous peritoneal access ports and intravenous 50 mg/m(2) of PTX at day 1 and day 8, meanwhile 80 mg/m(2) of Tigio was orally administered per day for 14 consecutive days, followed by 7 days of interval. Follow-up ended on December 15, 2019. Results: Of these 8 patients with recurrence of peritoneal metastasis after gastric cancer surgery, 1 case underwent laparotomy and loop stoma of terminal ileum because of complete colonic obstruction, and the remaining 7 cases underwent laparoscopy successfully and the recurrence of peritoneal metastasis was clearly diagnosed. Two patients with ovarian metastasis underwent laparoscopic bilateral adnexectomy. The median follow-up time was 17.5 (1.5 to 39.0) months, the median number of BIPS chemotherapy course was 11 (1 to 30), and the median survival time (MST) after BIPS chemotherapy was 17.0 months. The major adverse reaction in BIPS treatment was mainly myelosuppression, of which grade 3/4 leukopenia and neutropenia developed in 1 and 2 cases respectively. No BIPS-related death occurred. The MST of gastric cancer after radical gastrectomy was 40.0 months. Conclusions: Laparoscopy is a safe and feasible method for diagnosing the recurrence of peritoneal metastasis of gastric cancer. BIPS chemotherapy is effective and safe for its treatment and deserves further study.

Monitoring of optical emissions in laser cladding of 316L stainless steel.

Laser cladding is so complex that small disturbances may cause defects. Developing on-line monitoring technology for laser cladding is thus a priority task. Compared with expensive spectrometers and high-speed cameras, an economical optical sensing system based on two different photodiodes was established to optimize laser parameters and help monitor abnormal working conditions. In order to find optimal parameters, a series of experiments was carried out under different operating parameters such as laser power, scanning speed, and powder feeding rate. A practical rule is summarized to optimize process parameters by analyzing the time domain characteristics of the optical signal. Several experiments under different working conditions were performed to detect abnormal working conditions. Not only can an abnormal situation be recognized, but its type can also be distinguished by analyzing optical signals in the time and frequency domains. The optical sensing system provides a better understanding and accurate evaluation of laser cladding.

A novel FGFR1-binding peptide attenuates the degeneration of articular cartilage in adult mice.

OBJECTIVE: We previously reported that genetic ablation of (Fibroblast Growth Factors Receptors) FGFR1 in knee cartilage attenuates the degeneration of articular cartilage in adult mice, which suggests that FGFR1 is a potential targeting molecule for osteoarthritis (OA). Here, we identified R1-P1, an inhibitory peptide for FGFR1 and investigated its effect on the pathogenesis of OA in mice induced by destabilization of medial meniscus (DMM). DESIGN: Binding ability between R1-P1 and FGFR1 protein was evaluated by enzyme-linked immuno sorbent assay (ELISA) and molecular docking. Alterations in cartilage were evaluated histologically. The expression levels of molecules associated with articular cartilage homeostasis and FGFR1 signaling were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC). The chondrocyte apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. RESULTS: R1-P1 had highly binding affinities to human FGFR1 protein, and efficiently inhibited extracellular signal-regulated kinase (ERK)1/2 pathway in mouse primary chondrocytes. In addition, R1-P1 attenuated the IL-1ß induced significant loss of proteoglycan in full-thickness cartilage tissue from human femur head. Moreover, this peptide can significantly restore the IL-1ß mediated loss of proteoglycan and type II collagen (Col II) and attenuate the expression of matrix metalloproteinase-13 (MMP13) in mouse primary chondrocytes. Finally, intra-articular injection of R1-P1 remarkably attenuated the loss of proteoglycan and the destruction of articular cartilage and decreased the expressions of extracellular matrix (ECM) degrading enzymes and apoptosis in articular chondrocytes of mice underwent DMM surgery. CONCLUSIONS: R1-P1, a novel inhibitory peptide for FGFR1, attenuates the degeneration of articular cartilage in adult mice, which is a potential leading molecule for the treatment of OA.

LncRNA HULC triggers autophagy via stabilizing Sirt1 and attenuates the chemosensitivity of HCC cells.

Considerable evidences have shown that autophagy has an important role in tumor chemoresistance. However, it is still unknown whether the lncRNA HULC (highly upregulated in liver cancer) is involved in autophagy and chemoresistance of hepatocellular carcinoma (HCC). In this study, we for the first time demonstrated that treatment with antitumor reagents such as oxaliplatin, 5-fluorouracil and pirarubicin (THP) dramatically induced HULC expression and protective autophagy. Silencing of HULC sensitized HCC cells to the three antitumor reagents via inhibiting protective autophagy. Ectopic expression of HULC elicited the autophagy of HCC cells through stabilizing silent information regulator 1 (Sirt1) protein. The investigation for the corresponding mechanism by which HULC stabilized Sirt1 revealed that HULC upregulated ubiquitin-specific peptidase 22 (USP22), leading to the decrease of ubiquitin-mediated degradation of Sirt1 protein by removing the conjugated polyubiquitin chains from Sirt1. Moreover, we found that miR-6825-5p, miR-6845-5p and miR-6886-3p could decrease the level of USP22 protein by binding to the 3'-untranlated region of USP22 mRNA. All the three microRNAs (miRNAs) were downregulated by HULC, which resulted in the elevation of USP22. In addition, we showed that the level of HULC was positively correlated with that of Sirt1 protein in human HCC tissues. Collectively, our data reveals that the pathway 'HULC/USP22/Sirt1/ protective autophagy' attenuates the sensitivity of HCC cells to chemotherapeutic agents, suggesting that this pathway may be a novel target for developing sensitizing strategy to HCC chemotherapy.

Novel stent in the palliation of malignant esophageal strictures: a retrospective study.

The placement of metal stents is often used as a palliative treatment for malignant esophageal stenosis. We designed a novel stent that has been used clinically since 2011, and we therefore performed a retrospective study to compare the therapeutic effects of this novel metal stent to a conventional partially covered metal stent in patients with malignant esophageal strictures. The records of 201 consecutive patients who underwent placement of either the conventional partially covered metal stents (Group A, n = 92) or the new metal stents (Group B, n = 109) in the Endoscopy Center of General Hospital of Chengdu Military Command from October 2008 to March 2013 were reviewed. The median dysphagia score significantly improved in both groups 1 week following stent placement (P < 0.001). No significant differences were observed in success rate (P = 0.910) or the complication rate (P = 0.426) between groups. Six months after stent placement, recurrent dysphagia due to stent migration, tissue ingrowth or overgrowth or food obstruction occurred in 45% and 29% of patients in the conventional stent and new stent groups, respectively. The results of this retrospective study indicate that the new modified self-expandable metal stents (SEMS) is at least as safe and effective as the conventional partially covered SEMS in treatment of malignant esophageal strictures.

[Direct anterior approach versus posterolateral approach for total hip arthroplasty in the lateral decubitus position].

Objective: To compare the clinical efficacy of the direct anterior approach (DAA) and the posterolateral approach (PLA) for total hip arthroplasty (THA) in the lateral decubitus position. Methods: From July to December, 2014, 104 patients randomly divided into two equal groups of the DAA group and the PLA group underwent unilateral primary THA procedures.All procedures were performed by the same surgeon in the Department of Orthopaedics, the Affiliated Anhui Provincial Hospital of Anhui Medical University.General data, perioperative index, postoperative function and radiological evaluation were recorded and statistically analyzed. Results: The patients had an average follow-up of 14 (range, 10-16) months.No significant differences were detected with respect to the operation time, incision length, preoperative Hb concentration and transfusion rate between two groups (P> 0.05 for all comparisons). However, there were significant differences associated with the intraoperative bleeding, postoperative drainage and postoperative Hb concentration in the two groups(P<0.05 for all comparisons). The DAA group showed significant superior outcomes compared with the PLA group in the Harris hip scores [(83.6±7.1) vs (79.8±6.6), P<0.05], WOMAC[ (28.9±6.1) vs (36.1±6.9), P<0.001], and VAS pain scores[ (2.2±0.9) vs (2.9±1.1), P<0.05]at 1 month after surgery. No differences were seen between the study groups in the evaluation of radiography and the incidence of adverse event (P> 0.05 for all comparisons). Conclusions: Compared with the posterolateral approach, the present study shows the exciting results in patients underwent the DAA THA in the lateral decubitus position at early follow-up.The advantages of THA using the DAA include less operative trauma, alleviation of postoperative pain, and faster postoperative rehabilitation. It is a safe, reliable and effective surgery approach.

Upregulated microRNA-301a in osteosarcoma promotes tumor progression by targeting CDC14A.

MicroRNAs (miRs) are associated with tumor progression in various cancers, such as gastric and hepatic carcinomas, and lung cancer. miR-301a is overexpressed and displays oncogenic activity in cancers. We investigated the biological involvement of miR-301a in osteosarcoma (OS). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze expression levels of miR-301a in 24 OS and matched adjacent non-tumor tissues. A miR-301a mimic was transferred into OS cell lines U-2 OS and MG-63 to upregulate miR-301a. The effects of miR-301a were investigated by examining cell proliferation, migration, and the cell cycle. The miR-301 target was predicted by TargetScan and confirmed by western blotting and qRT-PCR. The expression of miR-301a was significantly higher in OS tissues compared with the matched adjacent non-tumor tissues (0.959 ± 0.39 vs 3.9516 ± 1.18). Upregulated miR-301a significantly increased proliferation at 48 and 72 h compared to the negative control (U-2 OS: 2.11 ± 0.21 vs 2.88 ± 0.24; 2.70 ± 0.26 vs 3.71 ± 0.24; MG-63: 2.19 ± 0.20 vs 3.19 ± 0.22; 3.1 ± 0.25 vs 4.01 ± 0.27) and migration capability (U-2 OS: 100 ± 20.19 vs 150.68 ± 32.83; MG-63: 100 ± 17.20 vs 133.35 ± 26.26), and decreased apoptosis in both U-2 OS (10.87 ± 2.53 vs 4.01 ± 2.23) and MG-63 (15.26 ± 2.15 vs 8.25 ± 3.07). The cell cycle studies revealed that miR-301a caused an increase of the G2 population in U-2 OS (38.6 ± 6.58 vs 47.2 ± 7.27) and MG-63 (44.01 ± 5.28 vs 57.9 ± 4.25). Additional experiments indicated that CDC14A was upregulated by miR-301a (0.63 ± 0.06 vs 0.98 ± 0.06; 1.49 ± 0.25 vs 2.99 ± 0.14). Overexpressed miR-301a may increase CDC14A expression and promote cell proliferation and migration in OS cells. Therefore, miR- 301a may be useful for osteosarcoma diagnosis and therapy.

Inflammatory dentigerous cyst of mandibular first premolar associated with endodontically treated primary first molar: a rare case report.

AIM: Inflammatory dentigerous cysts usually occur in the mixed dentition. It has been reported that inflammatory lesions from the root area of a deciduous tooth bring about the development of dentigerous cysts around the unerupted permanent tooth bud. Endodontic treatment is a common and successful procedure for periapical inflammation in children. An inflammatory dentigerous cyst can occur in conjunction with endodontically treated primary tooth. CASE REPORT: This article reports a case of 6 years and 6 months old boy, with a single, well-defined, unilocular, radiolucent area enclosing the first right unerupted mandibular premolar, accidentally discovered on the panoramic radiograph. The first right primary molar had received a root canal treatment 18 months prior. Clinical findings combined with radiographic and microscopic examinations confirmed the diagnosis of inflammatory dentigerous cyst. As treatment, enucleation of the cyst with removal of the involved permanent tooth was chosen and a removable partial denture was supplied to the patient after surgery. The 5-year follow-up revealed good healing of the bony lesion and displaced teeth. CONCLUSION: This case presented a severe and rare complication of endodontically treated primary tooth, and the recommendation includes: (1) early diagnosis of dentigerous cysts, which is essential to prevent extensive treatment; (2) more information on the adverse side effects of an endodontic treatment should be given to patients and parents; (3) patients should be informed about the importance of follow-ups and radiographic follow-up should be routinised.

Decreased microRNA-143 expression and its tumor suppressive function in human oral squamous cell carcinoma.

MicroRNA-143 serves as a tumor suppressor in many human malignancies. However, its involvement in oral squamous cell carcinoma (OSCC) is still unclear. In this study, we investigated the effects of miR-143 in OSCC tumorigenesis and development. Using real-time quantitative reverse transcription-polymerase chain reaction, we detected miR-143 expression in 109 pairs of human OSCC and adjacent noncancerous tissues. The associations between miR-143 expression and clinicopathological factors and prognosis of OSCC patients were also statistically analyzed. Further, the effects of miR-143 on the biological behavior of OSCC cells were investigated. miR-143 expression was significantly downregulated in OSCC tissue samples and cell lines. Decreased miR-143 expression was significantly associated with advanced T classifications, positive N classification, advanced TNM stage, and shorter overall survival. In addition, upregulation of miR-143 in Tca8113 cells reduced cell proliferation, invasion, and migration, as well as promoted cell apoptosis in vitro. These findings validate the clinical significance of miR-143 in OSCC and reveal that it may be an intrinsic regulator of tumor progression and a potential prognostic factor for this disease.

A Maltose-Binding Protein Fusion Construct Yields a Robust Crystallography Platform for MCL1.

Crystallization of a maltose-binding protein MCL1 fusion has yielded a robust crystallography platform that generated the first apo MCL1 crystal structure, as well as five ligand-bound structures. The ability to obtain fragment-bound structures advances structure-based drug design efforts that, despite considerable effort, had previously been intractable by crystallography. In the ligand-independent crystal form we identify inhibitor binding modes not observed in earlier crystallographic systems. This MBP-MCL1 construct dramatically improves the structural understanding of well-validated MCL1 ligands, and will likely catalyze the structure-based optimization of high affinity MCL1 inhibitors.

The novel BH-3 mimetic apogossypolone induces Beclin-1- and ROS-mediated autophagy in human hepatocellular carcinoma [corrected] cells.

Apogossypolone (ApoG2), a novel derivative of gossypol, exhibits superior antitumor activity in Bcl-2 transgenic mice, and induces autophagy in several cancer cells. However, the detailed mechanisms are not well known. In the present study, we showed that ApoG2 induced autophagy through Beclin-1- and reactive oxygen species (ROS)-dependent manners in human hepatocellular carcinoma (HCC) cells. Incubating the HCC cell with ApoG2 abrogated the interaction of Beclin-1 and Bcl-2/xL, stimulated ROS generation, increased phosphorylation of ERK and JNK, and HMGB1 translocation from the nucleus to cytoplasm while suppressing mTOR. Moreover, inhibition of the ROS-mediated autophagy by antioxidant N-acetyl-cysteine (NAC) potentiates ApoG2-induced apoptosis and cell killing. Our results show that ApoG2 induced protective autophagy in HCC cells, partly due to ROS generation, suggesting that antioxidant may serve as a potential chemosensitizer to enhance cancer cell death through blocking ApoG2-stimulated autophagy. Our novel insights may facilitate the rational design of clinical trials for Bcl-2-targeted cancer therapy.

Multiple variants of TERT and CLPTM1L constitute risk factors for lung adenocarcinoma.

Recent studies have shown that 5p15.33 is one of the chromosomal regions that is most consistently altered in lung cancer; common variants that are located in this region have been genotyped in various populations. However, the genetic contribution of these variants to carcinogenesis is relatively unknown. A clinic-based case-control study in Shanghai was undertaken on 196 patients with lung cancer and 229 healthy individuals. TERT rs2736100 and CLPTM1L rs401681 and rs402710 were genotyped using the ABI TaqMan Allelic Discrimination assay. For rs2736100, the G variant and the GG genotype were more frequent, whereas the TT genotype was less frequent in patients with lung adenocarcinoma than in controls. The CT genotype at rs401681 was more common and the TT genotype was rare in patients, and the differences were significant between lung adenocarcinoma patients and controls. This was also true for rs402710. Moreover, the frequency of the GGCTCT haplotype was higher and the TTTTTT frequency was lower in patients, especially those with lung adenocarcinoma. Aberrant linkage disequilibrium among the three SNPs was found in patients with lung adenocarcinoma. We conclude that multiple variants at 5p15.33 contribute to susceptibility to lung adenocarcinoma.

Surgical vs general practitioner assessment: diagnostic accuracy in 2-week-wait colorectal cancer referrals.

AIM: It has been recommended that patients with suspected colorectal cancer should proceed straight to an endoscopic test to increase speed of diagnosis, using only the information in the general practitioner's referral letter. This study aims to establish whether the diagnostic accuracy of the first surgical outpatient assessment is significantly greater than the general practitioner's assessment and if so by what means. METHOD: Demographic variables, symptoms and signs were collected from the first surgical outpatient assessment letters and the general practitioners' referral letters in 2-week-wait colorectal cancer referrals made between 2002 and 2005. Multiple logistic regression models derived from both the surgeons' and the general practitioners' letters were compared with receiver operator characteristic curves. RESULTS: Variables were collected from 978 2-week-wait colorectal cancer referrals. The median age was 69 years (range 19-98) and the male to female ratio was 1:2. Seventy-eight referrals were diagnosed with colorectal cancer. Surgeons' models demonstrated significantly greater diagnostic accuracy than general practitioners' models (area under the curve, 0.84 vs 0.73; P < 0.003). General practitioners' letters contained significantly less information than surgeons' letters (P < 0.001), but correcting for this did not account for the difference in diagnostic accuracy. The single variable that accounted for the difference in diagnostic accuracy was examination of the rectum by rigid sigmoidoscopy. CONCLUSION: Rigid sigmoidoscopy significantly improves the diagnostic accuracy of clinical assessment in patients with suspected colorectal cancer. If rigid sigmoidoscopy were omitted in a straight-to-test pathway, some patients would be denied the opportunity for immediate diagnosis.

Liver transplantation for hepatitis B virus-related hepatocellular carcinoma: one center's experience in China.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common and the third most deadly cancer worldwide, with more than half a million identified cases and about a similar number of subjects succumb to it each year. This study sought to evaluate our results of liver transplantation for HCC to identify prognostic factors. METHODS: Between December 2001 and December 2006, 224 patients (205 men, 19 women; age range, 15-75 years) with HCC underwent orthotopic liver transplantation (OLT) at our center. All grafts were from deceased donors. There were 68 cases within Milan criteria (30.3%), 32 cases beyond Milan criteria but within UCSF (University of California, San Francisco) criteria (14.3%), and 124 cases beyond UCSF criteria (55.4%). RESULTS: The overall 1-, 3-, and 5-year patient cumulative survival rates were 82.5%, 60.1%, and 51.5%, respectively. The survival rates were comparable between patients within Milan and UCSF criteria, but were significantly greater than that of patients beyond UCSF criteria. Multivariate analysis revealed alpha fetoprotein (AFP) >or= 800 microg/L, vascular invasion, and poor tumor differentiation to be independent prognostic factors. CONCLUSION: OLT is a safe and effective treatment for hepatitis B virus-related HCC. Compared with Milan criteria, UCSF criteria successfully expanded the indication without deteriorating the prognosis significantly, while preoperative AFP >or= 800 microg/L, vascular invasion, and poor tumor differentiation indicated poor survival.

Induction treatment of proliferative lupus nephritis with leflunomide combined with prednisone: a prospective multi-centre observational study.

To evaluate the efficacy and safety of leflunomide in the treatment of proliferative lupus nephritis, a prospective multi-centre observational study was conducted. Patients with biopsy proven proliferative lupus nephritis were assigned to receive either leflunomide or cyclophosphamide with concomitant prednisone. Leflunomide was given orally with a loading dose of 1 mg/kg/day for 3 days followed by 30 mg/day. Intravenous cyclophosphamide was administered monthly at a dose of 0.5 g/m2 of body-surface area. A total of 110 patients were enrolled, 70 in the leflunomide group and 40 in the cyclophosphamide group. The complete remission rate in the leflunomide group was 21% and partial remission rate 52%, as compared with 18% and 55%, respectively, in the cyclophosphamide group. Renal parameters and systemic lupus erythematosus disease activity index improved significantly and similarly in both groups. Serum creatinine decreased or stabilized in both treatment groups. No significant difference was noted with respect to clinical outcome between groups. Repeat biopsy also showed a significant reduction of active lesions in kidney pathology after 6 months of leflunomide treatment. Major adverse events, similar in both treatment groups, included infection, alopecia and hypertension. Leflunomide, compared with cyclophosphamide, in combination with prednisone was effective in the induction therapy of proliferative lupus nephritis and was generally well-tolerated.

Effect of hereditary obesity on renal expressions of NO synthase, caveolin-1, AKt, guanylate cyclase, and calmodulin.

BACKGROUND: Obesity has emerged as a major cause of diabetes, cardiovascular disease, and renal insufficiency worldwide. Obese Zucker rats exhibit hyperphagia, obesity, insulin resistance, hyperlipidemia, and glomerulosclerosis and are frequently used as a model to study hereditary form of metabolic syndrome. Nitric oxide plays a major role in preservation of renal function and structure. The present study was designed to test the hypothesis that renal disease in this model may be associated with down-regulation of endothelial (eNOS) and neuromal NO synthases (nNOS) in the kidney. The study further sought to explore expressions of caveolin-1, phospho AKt, and calmodulin, which regulate activities of constituitive NOS isoforms, as well as soluble guanylate cyclase (sGC), which is involved in NO signaling. METHODS: Twenty-two-week-old male obese and lean Zucker rats were studied. Body weight, serum lipids, urine albumin excretion, and renal tissue abundance of the above proteins were determined. RESULTS: Serum glucose and arterial pressure were unchanged, whereas urinary NO metabolite (NO(chi)) excretion and renal tissue nitrotyrosine abundance were markedly reduced (denoting depressed NO production) in the obese versus lean Zucker rats. This was accompanied by significant glomerulosclerosis, tubulointerstitial damage, renal immune cell infiltration, marked down-regulations of renal tissue eNOS and nNOS, mild reduction of caveolin-1, and unchanged calmodulin, phospho-AKt, and sGC. CONCLUSION: Hereditary obesity can result in down-regulations of kidney eNOS and nNOS, marked reduction of NO production, and glomerulosclerosis prior to the onset of frank diabetes and hypertension.

Vascular endothelial growth factor and its receptor Flk-1 are expressed in the hippocampus following entorhinal deafferentation.

Vascular endothelial growth factor (VEGF) has been thought of as a mitogen that promotes proliferation of endothelial cells and as a neurotrophic factor that stimulates neurogenesis and axonal growth in both peripheral and central nervous systems. To investigate the potential involvement of VEGF in the lesion-induced reorganization in the brain, the expression changes of VEGF and its receptor Flk-1 were analyzed in the mouse hippocampus after transections of the entorhinal afferents. In situ hybridization and immunohistochemistry showed the time-dependent expression upregulation of VEGF mRNA and protein in the entorhinally denervated hippocampal stratum lacunosum-moleculare and dentate outer molecular layer, which initiated by 3 days postlesion, reached its maximum at 7-15 days postlesion, still persisted by 30 days postlesion for protein, and recovered to the normal levels at 30 days postlesion for mRNA and at 60 days postlesion for protein. Double labeling of VEGF and glial fibrillary acidic protein revealed that VEGF-expressing cells in the denervated areas were reactive astrocytes. Semi-quantitative RT-PCR analysis showed that VEGF receptor Flk-1 mRNA was also time-dependently upregulated in the deafferented hippocampus with its maximal elevation at 7-15 days postlesion while the Flt-1 mRNA levels remained unchanged at any time point we examined. Immunohistochemistry analysis also displayed the upregulation of Flk-1 protein in the denervated stratum lacunosum-moleculare and outer molecular layer with a time course similar to that of VEGF mRNA upregulation. Flk-1 receptors were found to be expressed not only by reactive astrocytes but also by neurites, which most likely belong to sprouting axons by 7 days postlesion and regrowing dendrites by 15-30 days postlesion. From these data we suggest that the spatiotemporal upregulation of VEGF and Flk-1 in the hippocampus is induced by entorhinal deafferentation and that VEGF may be involved in the structural reorganization in the deafferented hippocampus via directly or indirectly promoting neurite growth.

Expression of NOX-I, gp91phox, p47phox and P67phox in the aorta segments above and below coarctation.

Aorta coarctation results in hypertension (HTN) in the arterial tree proximal to stenosis and, as such, provides an ideal model to discern the effects of different levels of blood pressure on the vascular tissue in the same animal. Compelling evidence has emerged supporting the role of oxidative stress as a cause of HTN. However, whether or not HTN (independent of the circulating humoral factors) can cause oxidative stress is less certain. NAD(P)H oxidase isoforms are the main source of reactive oxygen species (ROS) in the vascular tissues. We therefore compared the expressions of NOX-I, gp91phox and the regulatory subunits of the enzyme in the aorta segments residing above and below coarctation in rats with abdominal aorta banding. Rats were studied 4 weeks after aorta banding above the renal arteries or sham operation. Subunits of NAD(P)H oxidase and its NOX-I isoform as well as endothelial NO synthase (eNOS) and nitrotyrosine (footprint of NO oxidation by superoxide) were measured in the aorta segments above and below coarctation. The gp91phox, p47phox, and p67phox subunits of NAD(P)H oxidase, NOX-I isoform, eNOS and nitrotyrosine were markedly increased in the aorta segment above coarctation (hypertensive zone), but were virtually unchanged in the segment below coarctation. Since, excepting blood pressure, all other conditions were constant, the upregulation of NAD(P)H oxidase isoforms and the increased NO oxidation in the aorta segment above, but not below, coarctation prove that HTN, per se, independent of circulating mediators can cause oxidative/nitrosative stress in the arterial wall. These observations suggest that HTN control may represent a specific form of antioxidant therapy for hypertensive disorders.