[Analysis of clinical manifestations and prognosis of primary systemic light chain amyloidosis with liver involvement].

Objective: To summarize the clinical manifestations and prognostic factors of patients with hepatic amyloidosis in a single center. Methods: The clinical data of 28 primary systemic light chain amyloidosis cases with liver involvement in our center from October 2012 to January 2023 were retrospectively analyzed. The main clinical manifestations and prognostic factors were studied. Statistical analysis were performed using the χ(2) test, Fisher's exact test, Wilcoxon rank test, or Kaplan-Meier survival curve log-rank test according to the different data. Results: The main clinical manifestations of patients with liver involvement were abdominal distension, hepatomegaly, and edema. CD56 and chemokine receptor 4 protein expression accounted for 52% (13/25) and 56% (14/25). 64.3% (9/14) patients were combined with t (11,14), and 21.4% (3/14) patients were positive for 1q21 (+), and no patients were detected with del(17p). Univariate analysis showed that Mayo 2004 and 2012 stages and total bilirubin (TBil) ≥34.2 µmol/L were associated with progression-free survival and overall survival. The median progression-free survival and overall survival were significantly inferior in patients with TBil≥34.2µmol/L group (0.178 years, 0.195 years) than with the TBil<34.2µmol/L group (0.750 years, 3.586 years) (P < 0.05). Conclusion: Mayo stage and hyperbilirubinemia are inferior prognostic factors for patients with primary systemic light chain amyloidosis accompanied with liver involvement.

[Correlation between C-reactive protein to albumin ratio and restenosis after femoral popliteal stenting in patients with lower extremity arteriosclerotic obliterans].

Objective: To investigate the study of the correlation between C-reactive protein to albumin ratio (CAR) and restenosis after stenting in patients with lower extremity atherosclerotic occlusive disease(LEASO). Methods: The clinical data of 95 patients with LEASO admitted to the Department of Vascular Surgery of Nanjing Drum Tower Hospital from June 2020 to December 2022 were retrospectively analyzed. There were 67 males and 28 females,aged (73.1±9.4) years (range:51 to 92 years). The patients were classified into the restenosis group (n=61) and the patency group (n=34) according to the CT angiography results. Independent sample t test,Mann-Whitney U test and χ2 test were used to compare the data between two groups. Risk factors for restenosis after femoropopliteal artery stenting in patients with LEASO were analyzed using multivariate Cox regression. The relationship between preoperative CAR level and restenosis after stent placement was analyzed. Subject operating characteristic(ROC) curves of CAR were plotted to assess the predictive value of CAR for restenosis after stenting,and the results were expressed as area under the curve (AUC). Results: The aortoiliac calcification grade,number of stents,length of stents,C-reactive protein and CAR levels in restenosis group were higher than those in the patency group,and the serum albumin level was lower than that in the patency group(all P<0.05). And the results of multifactorial Cox regression analysis showed that higher pre-procedure CAR level and lower ABI value was an independent risk factor for in-stent restenosis. The AUC of the ROC curve for restenosis was 0.737(95%CI:0.617 to 0.856),the AUC of the ROC curve for 12-month restenosis was 0.709(95%CI:0.602 to 0.815), and the AUC of the ROC curve for 24-month restenosis was 0.702(95%CI:0.594 to 0.811). Conclusion: Higher pre-procedural CAR levels in patients with LEASO is risk factor for in-stent restenosis,and CAR has a predictive value for restenosis after lower extremity arterial stent dilatation and angioplasty.

[Clinical analysis of surgical treatment of infection after interventional operation for major iliac artery disease in 6 cases].

Objective: To explore the surgical treatment strategy of stent graft infection after interventional treatment of major iliac artery related diseases. Methods: Retrospective analysis was performed on the clinical data of 6 patients with secondary stent graft infection after interventional treatment for major iliac artery related diseases admitted to the Department of Vascular Surgery,Affiliated Drum Tower Hospital,Medical School of Nanjing University from November 2021 to August 2022.There were 5 males and 1 female,with a mean age of 64 years (range:49 to 79 years).The infection time was 53 to 3 165 days.All the 6 patients received surgical treatment,including 3 patients who underwent anatomic bypass grafting (axillary arterial-femoral artery bypass,femoral arterial-femoral artery bypass) using artificial vessels,and 3 patients who underwent in situ abdominal aorta reconstruction using bovine pericardium.The perioperative situation,postoperative infection and the occurrence of serious adverse events were recorded,and the safety of different treatment methods and materials was evaluated. Results: All patients successfully completed the operation and no death occurred during hospitalization.Intraoperative blood loss was 2 000~5 000 ml,and intraoperative blood transfusion was 1 600 to 5 350 ml.All the patients were followed up for 81 to 395 days after surgery,and the incision healed well,and no reinfection occurred.Postoperative gastrointestinal bleeding occurred in 1 patient,secondary surgery (retroperitoneal hematoma removal) was performed in 1 patient due to postoperative bleeding at the vascular anastomosis,both lower limb amputations were performed in 1 patient due to postoperative lower limb ischemia,and intermittent claudication occurred in 2 patients.All patients were alive at the last follow-up. Conclusion: For patients with aortic stent graft infection,when the infection is not serious and there is enough space to block the proximal and distal aorta,in situ aortic reconstruction is an effective treatment,and different materials can achieve satisfactory results in a short period of time.

[Application of meandering mesenteric artery in vascular surgery].

In recent years, the therapeutic concepts and surgical methods of the meandering mesenteric artery involved in atherosclerosis have been reported in the literature, and the importance of this lateral branch circulation in the field of vascular surgery has received more attention. With the improvement of imaging techniques, the discovery rate of this collateral circulation increased. In the presence of major iliac artery occlusion, the meandering mesenteric artery may serve as an important collateral circulation to relieve ischemia in the visceral or lower extremities. The meandering mesenteric artery may also lead to type Ⅱ internal leakage after endovascular repair, while the embolization of inferior mesenteric artery may be performed through the meandering mesenteric artery. The role of meandering mesenteric arteries in vascular surgery needs further study.

[Effect of low density carotid plaque on the development of cerebral small vessel disease in patients with carotid stenosis].

Objective: To investigate the correlation between cerebral small vessel disease (CSVD) and carotid low-density plaque on multi-slice spiral CT angiography (MSCTA) in patient with carotid stenosis. Methods: The clinical data of 221 patients with carotid stenosis who admitted to Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, from January 2016 to January 2021 were retrospectively analyzed. There were 195 males and 26 females, with the age of (70.0±8.4) years (range: 48 to 88 years). According to MRI, the patients were divided into carotid stenosis combined with CSVD group (the CSVD group) and carotid stenosis without CSVD group (the non-CSVD group). Lowest density in the carotid atherosclerotic plaque area (CAPALD) was analyzed by MSCTA. The t-test, Mann-Whitney U test and Chi-square test were used for comparison between the two groups. Univariate and multivariate Logistic regression analysis were performed on CAPALD and other clinical indicators with CSVD. Receiver operating characteristic (ROC) curves of CAPALD and CAPALD combined with the demographics (sex, age and body mass index) were plotted for predicting CSVD, and the area under the curve (AUC), sensitivity and specificity were calculated. Results: There were 169 patients in the CSVD group and 52 patients in the non-CSVD group. In the CSVD group, 88.8% (150/169) were males and 11.2% (19/169) were females, with the age of (70.5±8.2) years (range: 48 to 88 years). In the non-CSVD group, 86.5% (45/52) were males and 13.5% (7/52) were females, with the age of (68.4±9.1) years (range: 51 to 85 years). CAPALD and the score of Montreal cognitive assessment were lower in the CSVD group than those in the non-CSVD group (21.0 HU vs. 35.0 HU, Z=-3.760, P<0.01; 22.6±3.9 vs. 24.8±3.3, t=-2.064, P<0.05). Multivariate Logistic regression analysis showed that CAPALD was an independent factor for CSVD (OR=1.044, 95%CI:1.020 to 1.070, P<0.01). The AUC of the ROC curve for CAPALD predicting carotid stenosis with CSVD was 0.672 (P<0.01), with cut-off value of 34.5 HU, sensitivity of 82.8%, and specificity of 50.0%. The AUC of ROC curve for CAPALD combined with the demographics predicting CSVD was 0.733 (P<0.01), with sensitivity of 82.9% and specificity of 64.0%. Conclusions: The decreased CAPALD is a risk factor for CSVD in patients with carotid stenosis. The analysis of carotid plaque density by MSCTA may help to identify the patients at high risk of CSVD.

[Influencing factors for postoperative survival of patients with pneumoconiosis treated by lung transplantation].

Objective: To explore the influencing factors for postoperative survival of patients with pneumoconiosis (silicosis) after lung transplantation in order to improve their clinical outcomes. Methods: In August 2021, retrospective alalysis from December 2015 to July 2021, 29 patients with end-stage pneumoconiosis underwent lung transplantation at Department of Thoracic Surgery, Affiliated Henan Provincial People's Hospital, Zhengzhou University. The survival, postoperative complications, and causes of death were analyzed. Life table and Kaplan-Meier method were used to draw survival curves, the log-rank test was used to compare the influence of each factor on survival rates, and the multivariate Cox proportional hazards regression model was used to evaluate the influence of each factor on survival. Results: All the patients underwent successful lung transplantation, with survival rates of 75% at 6 months, 70% at 1 year, 65% at 2 years, 50% at 3 years and 50% at 5 years. The Kaplan-Meier survival analysis showed that BMI, age and preoperative albumin level were influencing factors for postoperative survival rates (P<0.05) . The multivariate COX regression model showed that BMI≥18.5 kg/m(2) and the albumin level≥35 g/L were the protective factors (P<0.05) . Conclusion: Aging older, preoperative BMI<18.5 kg/m(2) and hypoalbuminemia are independent risk factors for death after lung transplantation. Survival rates are affected by preoperative BMI index, albumin level and age. Early intervention should be made before lung transplantation to promote the BMI index and albumin level to reach the standard.

LncRNA KCNQ1OT1 contributes to the cisplatin resistance of tongue cancer through the KCNQ1OT1/miR-124-3p/TRIM14 axis.

OBJECTIVE: Tongue cancer is a common malignant tumor in the oral and maxillofacial region, most of which is squamous cell carcinoma. Cisplatin (DDP) is one of the chemotherapy drugs for patients with tongue squamous cell carcinoma (TSCC). However, DDP resistance has become a major obstacle to its clinical application. Our study aimed to investigate the effects of long non-coding RNA (lncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) on DDP resistance of tongue cancer and the underlying mechanism. PATIENTS AND METHODS: The levels of KCNQ1OT1, miR-124-3p, and tripartite motif containing 14 (TRIM14) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The maximum size of tumor (MTS) assay was used to detect the cell survival rates. Furthermore, the cell proliferation was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Transwell assay was performed to detect the cell migration and invasion. Western blot assay was used to detect the protein levels of Vimentin, N-cadherin, E-cadherin, and TRIM14. The functional targets of KCNQ1OT1 and miR-124-3p, miR-124-3p and TRIM14 were predicted by starBase 3.0 and TargetScan. The relationship between KCNQ1OT1 and miR-124-3p was confirmed by Dual-Luciferase reporter assay, RNA immunoprecipitation (RIP) and RNA pull-down. Further, the relationship between miR-124-3p and TRIM14 was verified by Dual-Luciferase reporter assay. Animal experiment revealed the effect of KCNQ1OT1 on DDP resistance of tongue cancer cells in vivo. RESULTS: KCNQ1OT1 was upregulated in DDP-resistant tongue cancer tissues and cells, and mainly expressed in cytoplasm. Functionally, the knockdown of KCNQ1OT1 inhibited the survival rate, proliferation, migration, invasion, and EMT of the DDP-resistant tongue cancer cells. Of note, miR-124-3p acted as a target of KCNQ1OT1 and KCNQ1OT1 could reduce the expression of miR-124-3p. Moreover, miR-124-3p targeted TRIM14 and the downregulation of TRIM14 reduced the DDP resistance of tongue cancer cells. Importantly, KCNQ1OT1 regulated the TRIM14 expression by targeting miR-124-3p. Furthermore, KCNQ1OT1 knockdown reduced the DDP-resistant tumor growth and weight through the miR-124-3p/TRIM14 axis in vivo. CONCLUSIONS: LncRNA KCNQ1OT1 promotes the DDP resistance of tongue cancer by sponging miR-124-3p to regulate TRIM14 expression.

[Influence factors of carotid endarterectomy improving vascular cognitive impairment].

Objective: To investigate the influence factors of carotid endarterectomy(CEA) improving cognitive function in patients with carotid stenosis. Methods: The clinical data of carotid stenosis patients with cognitive impairment who underwent CEA in Nanjing Drum Tower Hospital and the First People's Hospital of Lianyungang from December 2011 to July 2017 were retrospectively analyzed. One week before operation, carotid CT angiography and cranial magnetic resonance imaging were performed, and the cognitive function of patients was evaluated with Montreal Cognitive Scale (MoCA). The magnetic resonance imaging and MoCA were reexamined 4 weeks after the procedure. The patients were divided into improved group (COI+) and un-improved group (COI-) according to whether the cognitive function score was improved or not after operation. The general data, carotid artery occlusiontime, surgical site, preoperative carotid calcification score (CS) and the Fazekas score, pre-operative and post-operative cerebral perfusion parameters, like mean transit time(MTT), time to peak(TTP) and arrivetime (T0), and any new infarcts after operation between the two groups were compared. Results: A total of 70 patients were selected, including 50 patients in group COI+ and 20 patients in group COI-. There were no significant differences in age, gender, hypertension, diabetes mellitus, smoking and drinking habits, as well as in carotid artery occlusiontime and preoperative Fazekas score between the two groups (all P>0.05). The preoperative carotid artery calcification scores of the two groups were 469.75±50.86 and 393.51±77.41, respectively. The changes of pre-and post-operation perfusion parameters between the two groups were statistically significant, with ΔMTT were 7.79±9.51 and 3.03±6.40, ΔTTP were 5.83±8.98 and 1.17±4.77, T0 were 5.89±8.08 and 3.05±5.95, respectively(t=4.844, 2.053, 2.192 and 1.423, respectively, all P<0.05). Proportion of cases with new infarcts after operation(0.38 vs 0.65) or undergoing left CEA (0.66 vs 0.40)between the two groups was statistically different (χ(2)=4.197 and 9.677, respectively, both P<0.05). Conclusion: Higher preoperative CS score, undergoing left CEA, significantly improved cerebral perfusion and without new infarct postoperatively, are independent factors contributing to improving cognitive function through CEA operation.

[Research advances in the aortic remodeling after thoracic endovascular aortic repair therapy of Stanford type B aortic dissection].

Aortic dissection is one of the most common vascular emergent disease. Thoracic endovascular aortic repair (TEVAR) therapy which created the new era of treatment of Stanford type B aortic dissection (TBAD) has gradually replaced the surgical treatment and becomes the gold standard for treatment of TBAD. Aortic remodeling after TEVAR is the key factor to evaluate the mid-term survival rate and successful treatment of the aortic dissection victims. However, there are few studies on aortic remodeling and lack of unified criteria to evaluate it. This article was to summarize the domestic and abroad research advances which focused on the morphological changes, the regularity, and the evaluation criteria of aorta remodeling after TEVAR.

[Clinical effectiveness of pleural abrasion in video-assisted thoracic surgery for bullae resection].

Objective: To evaluate the efficacy of pleural abrasion in treatment of spontaneous pneumothorax with video-assisted thoracic surgery (VATS) for bullae resection. Methods: The clinical data of 158 patients with initial spontaneous pneumothorax who underwent video-assisted thoracic wedge resections with or without pleural abrasion in Henan Provincial People's Hospital from June 2010 to June 2015 were retrospectively analyzed. The patients were assigned to two equal groups according to whether pleural abrasion was applied or not: experimental group (with pleural abrasion) and control group (without pleural abrasion); and there were 79 patients in each group.There were 62 males and 17 females aged 15-60 years (mean age 34 years) in pleural abrasion group. And there were 70 males and 9 females aged 18-60 years (mean age 38 years) in non-pleural abrasion group.After surgery, all patients were evaluated for postoperative pain, chest tube removal time, hospital stay and other complications.Independent samples t test was used to compare the data between groups. Results: Surgeries for 158 patients were performed successfully.No mortality occurred.There was no conversion to thoracotomy.Postoperative pain, operation time, intraoperative blood loss, chest tube removal time, pleural canals flowand average hospital stay in non-pleural abrasion group was significantly lower for 4.4, 19 minutes, 10 ml, 21 hours, 87 ml and 1.4 days respectively when compared with those in pleural abrasion group (t=32.478, 7.140, 11.093, 7.288, 10.246, 8.070, all P<0.05). There was no missing case with a follow-up of 30 months.No complications, such as pneumothorax, was observed. Conclusions: Postoperative pain, chest tube removal time and hospital stay in non-pleural abrasion group are all lower than those in pleural abrasion group.And there is no significant difference in the recurrence of pneumothorax between the two groups after VATS bullae resection.

Feedback intervention to doctors improves patient satisfaction among outpatients in Inner Mongolia Autonomous Region, China.

OBJECTIVES: The doctor-patient relationship (DPR) in China is known to be tense. We tested whether an intervention program providing individualized feedback to doctors by patients could improve patients' satisfaction in an outpatient setting. STUDY DESIGN: A non-randomized controlled prepost intervention study in a tertiary hospital. Six surgery clinics were chosen as the intervention group and eight internal medicine clinics as the control group. METHODS: Before the program started, patients attending each group of clinics were asked to fill in the Short-Form Patient Satisfaction Questionnaire (PSQ-18). In the experimental period, patients attending the intervention clinics were requested to rate their perception of the doctor's quality of care in various domains on an 8-question feedback card immediately after exiting from the examination room and to drop the completed card into the feedback box for the particular doctor. The cards were then collected by the doctor confidentially at the end of each day. There was no feedback in the control clinics. After the experimental period ended, the doctors in both groups of clinics were reassessed by a new series of patients using PSQ-18. The PSQ-18 scores were compared within the same group of clinics over time, and the changes in satisfaction score compared between intervention and control clinics. RESULTS: There were 189 and 190 responders in the intervention group and 190 and 200 in the control group, before and after the intervention period, respectively. Scores in all domains increased significantly (P < 0.001) in the intervention group but not in the control group. Significant improvement in the patient satisfaction scores in the intervention clinics compared with the control clinics was confirmed by mixed-effects linear regression controlling for the effects of gender, age, marital status, education, and household income in the domains of general satisfaction, technical quality, communication, and accessibility and convenience. CONCLUSIONS: Timely feedback to doctors of patients' perception of quality of care received can improve outpatient satisfaction in a Chinese hospital.

CpG Oligodeoxynucleotide1826 combined with radioresistant cancer cell vaccine confers significant antitumor effects.

Immunotherapy is a hot issue in cancer research over the years and tumor cell vaccine is one of the increasing number of studies. Although the whole tumor cell vaccine can provide the best source of immunizing antigens, there is still a limitation that most tumors are not naturally immunogenic. CpG Oligodeoxynucleotides (CpG ODNs), synthetic oligonucleotides containing a cytosine-phosphate-guanine(CpG) motif, was shown to enhance immune responses to a wide variety of antigens. In this study, we generated the radioresistant Lewis lung cancer cell by repeated X-ray radiation and inactivated it as a whole tumor cell vaccine to enhance the immunogenicity of tumor cell vaccine. Mice were subcutaneously immunized with this inactivated vaccine combined with CpG ODN1826 and then inoculated with autologous Lewis lung cancer (LLC) to estimate the antitumor efficacy. The results showed that the radioresistant tumor cell vaccine combined with CpG ODN1826 could significantly inhibit tumor growth, increased survival of the mice and with 20% of the mice surviving tumor free in vivo compared with the unimmunized mice bearing LLC tumor. A significant increase of apoptosis was also observed in the tumor prophylactically immunized with vaccine of inactivated radioresistant tumor cell plus CpG ODN1826. The potent antitumor effect correlated with higher secretion levels of tumor necrosis factor-alpha(TNF-α) and lower levels of interleukin-10(IL-10) concentration in serum. Furthermore, the results suggested that the antitumor mechanism was probably depended on the decreased level of programmed death ligand-1(PD-L1) which plays an important role in the negative regulation of immune response by the inhibition of tumor antigen-specific T cell activation. These findings clearly demonstrated that the radioresistant tumor cell vaccine combined with CpG ODN1826 as an appropriate adjuvant could induce effective antitumor immunity in vivo.

Effects of Carotid Endarterectomy on Cerebral Reperfusion and Cognitive Function in Patients with High Grade Carotid Stenosis: A Perfusion Weighted Magnetic Resonance Imaging Study.

OBJECTIVE: To investigate the influence of carotid endarterectomy (CEA) on cerebral perfusion and cognitive function in patients with internal carotid artery stenosis (ICA). METHODS: Patients were prospectively enrolled in this study. Shunted patients were excluded. Cerebral perfusion was measured by magnetic resonance (MR) perfusion weighted imaging (PWI) and diffusion weighted imaging (DWI) in 46 patients with >65% ICA (31 males, 64.5 ± 6.7 years) 1 week before and 6 weeks after CEA. Cognitive function was assessed using the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) 1 week before and 6 weeks after CEA. RESULTS: After CEA, perfusion parameters from PWI decreased, including mean transit time (MTT) (21.07 ± 7.36 vs. 14.27 ± 6.22, p < .0001), time to peak (TTP) (28.69 ± 8.54 vs. 23.45 ± 4.25, p = .001), arrive time (T0) (19.89 ± 7.32 vs. 15.20 ± 3.51, p = .001), and relative cerebral blood volume (rCBV) (11.48 ± 3.50 vs. 7.53 ± 3.17, p < .0001). A significant improvement was observed in MoCA (20.48 ± 1.70 vs. 22.04 ± 1.48, p = .001). Spearman's rank correlation analysis between TTP and MoCA scores demonstrated a linear relationship with an excellent correlation coefficient (R = -.893, p < .001). Linear regression indicated that diabetes was a risk factor for cognitive improvement in patients with ICA (p = .014). Further analysis showed that patients with DM performed worse in MoCA after the procedure (with-DM 21.15 ± 1.28 vs. non-DM 22.4 ± 1.46, p = .010) while the baselines were similar (non-DM: 20.3 ± 1.8 vs. with-DM: 20.9 ± 1.4, p = .362). CONCLUSION: CEA could improve the cerebral perfusion and the cognitive function in un-shunted ICA patients. Cerebral reperfusion was an important factor for cognitive improvement. Diabetes had a negative effect on cognitive improvement after CEA.

Knockdown of the inflammatory factor pentraxin-3 suppresses growth and invasion of lung adenocarcinoma through the AKT and NF-kappa B pathways.

Pentraxin-3 (PTX3), a modulator of tumor-associated inflammation, is known to be positively correlated with tumor grade and severity of malignancies, but the function and molecular underlying mechanisms of PTX3 remain unclear. In the present study, the expression of PTX3 in human lung adenocarcinoma (LAC) was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was performed to explore the effects of lentiviral vector-mediated PTX3 shRNA (Lv-shPTX3) on cell growth and invasive potential in LAC cell lines (A549 and LETPα-2), assessed by MTT and Transwell assays, respectively. We found that the expression of PTX3 protein was significantly increased in LAC tissues compared with that in adjacent non-cancerous tissues (ANCT) (60.42% vs. 29.17%, P=0.004), and positively correlated with lymphatic invasion of the tumor (P=0.006). Furthermore, knockdown of PTX3 suppressed tumor proliferation and invasion of LAC cells, followed by decreased expression of p-AKT, p-NF-kappa B, PCNA, and MMP-9. Taken together, our findings demonstrate that upregulation of PTX3 expression is correlated with tumor metastasis of LAC patients, and knockdown of PTX3 blocks the development of LAC through inhibition of the AKT and NF-kappa B pathways, suggesting that PTX3 may serve as a potential therapeutic target for the treatment of cancer.

[Hypoxia induced HIF-1 accumulation and VEGF expression in gastric epithelial mucosa cell: involvement of ERK1/2 and PI3K/Akt].

Hypoxia is a common environmental stress that influences signaling pathways and cells function, which through initiating intracellular signaling pathways and hence leading to the activation of the transcription factor hypoxia-inducible factor-1 (HIF-1). In this study, we initially confirm that hypoxia activates HIF-1alpha protein expression in a time-dependent manner with a maximum reached at 60 min in vitro and 4h in vivo in gastric mucosa epithelial cells. The expression of HIF-1alpha is correlated with the activation of HIF-1 DNA binding and transcriptional activity. Hypoxia dose not affect HIF-1alpha mRNA transcription but regulates HIF-1alpha protein expression through a translation-dependent pathway to regulate protein synthesis. Hypoxia could induce phosphorylation of Akt, MAPK (ERK), and target of p70S6K1. PI3K and MAPK inhibitor, LY294002 and U0126 could inhibit hypoxia-induced HIF-1 and VEGF expression. We also investigated the role of reactive oxygen species (ROS) involved in HIF-1 and VEGF expression Exogenous addition of H2O2 was sufficient to activate Akt and ERK, scavengers of H2O2 significantly inhibited hypoxia-induced Akt and ERK, and subsequent HIF-lax expression and transcriptional activity. In conclusion, our data suggested that hypoxia- PI3K signaling through Akt and ERK kinases regulated ROS-dependent, hypoxia- induced HIF-1 activation and VEGF expression in gastric mucosa epithelial cells.

Phospho Akt mediates multidrug resistance of gastric cancer cells through regulation of P-gp, Bcl-2 and Bax.

Phosphatidylinositol 3-kinase/Akt pathway is an important intracellular pathway that is frequently activated in cancer cells. The role of P-AKT in multidrug resistance of gastric cancer cells and the possible underlying mechanisms are here investigated. Up-regulation of P-AKT expression could confer resistance to both P-glycoprotein-related and P-glycoprotein-non-related drugs on AGS cells, and suppress adriamycin-induced apoptosis, along with decreased accumulation and increased releasing amount of adriamycin. P-AKT could significantly up-regulate the expression of Bcl-2, and down-regulate the expression of Bax, but not alter the expression of PTEN in gastric cancer cells. Inhibition of P-AKT expression could partially reverse P-AKT-mediated multidrug resistance and significantly up-regulate P53 expression, and down-regulate the expression of P-glycoprotein and the transcription of the multidrug resistance gene 1. Further studies of the biological functions of P-AKT may be helpful for understanding the mechanisms of multidrug resistance of gastric cancer and developing possible therapeutical strategies.

Overexpression of PrPC and its antiapoptosis function in gastric cancer.

Cellular prion protein (PrP(C)), a glycosylphosphatidylinositol-anchored membrane protein, was found in our lab to be widely expressed in gastric cancer cell lines. In order to evaluate its biological significance in human gastric cancer, we investigated its expression in a large series of gastric tissue samples (n = 124) by immuno histochemical staining with the monoclonal antibody 3F4. Compared with normal tissues, gastric adenocarcinoma showed increased PrP(C) expression, correlated with the histopathological differentiation (according to the WHO and Lauren classifications) and tumor progression (as documented by pTNM staging). To better understand the underlying mechanism, we introduced the PrP(C) and two pairs of RNAi into the poorly differentiated gastric cancer cell line AGS and found that PrP(C) suppressed ROS and slowed down apoptosis in transfected cells. Further study proved that the apoptosis-related protein Bcl-2 was upregulated whereas p53 and Bax were downregulated in the PrP(C)-transfected cells. A reverse effect was observed in PrP(C) siRNA-transfected cells. These results strongly suggested that PrP(C) might play a role as an effective antiapoptotic protein through Bcl-2-dependent apoptotic pathways in gastric cancer cells. Further study into the mechanism of these relationships might enrich the knowledge of PrP, better our understanding of the nature of gastric carcinoma, and further develop possible strategies to block or reverse the development of gastric carcinoma.

Zinc ribbon domain containing 1 protein: modulator of multidrug resistance, tumorigenesis and cell cycle.

Zinc ribbon domain containing 1 (ZNRD1) gene encoding a protein consisting of two zinc ribbon domains was recently cloned from the human HLA locus. So far, ZNRD1 has been found implicated in transcription regulation and might play potential roles in mediating several biological processes, including multidrug resistance, tumorigenesis and cell cycle. This article reviewed these recent findings and provided additional information to support the role of ZNRD1 gene as a novel candidate DNA damage repair related gene.

The impact of gastrocnemius muscle cell changes in chronic venous insufficiency.

OBJECTIVE: To investigate the pathological and metabolic changes in the gastrocnemius muscle in patients with chronic vein insufficiency (CVI). METHOD: Thirty-six patients with varicose veins were investigated by ambulatory venous pressure (AVP) and duplex ultrasonography. Twelve age and height-matched controls were used for comparison. Patients and controls consented to participate in this study. Twenty-one patients with primary vein varicose (group AI) and 15 patients (group AII) with primary deep venous valve incompetence (DVI) underwent biopsies of the gastrocnemius muscle during operation. Adductor biopsies obtained from the same limbs served as a control group (group B) and specimens from controls subjects without venous disease served as the second control group (group C). All the specimens were investigated by superoxide dismutase (SOD), nitric oxide (NO), Na+-K+-ATPase, Ca2+-ATPase and lactic acid (LD) determinations. Samples were subjected to light and electron microscopy following H & E staining, special ATPase, cytochrome oxidase/succinate dehydrogenase (COX/SDH) stains. RESULTS: Normal muscle architecture was seen following H & E, ATPase and COX/SDH staining and normal cell metabolism was observed in specimens of groups B and C. In group A, pathological changes were encountered in the gastrocnemius muscle including disseminated myofibril atrophy, cell denaturation and necrosis, inflammatory cell infiltration, proliferation and dilation of interfascicular veins. ATPase staining (pH 9.4) demonstrated grouping of atrophic fibres, especially type I myofibril grouping, accompanied by moderate to severe atrophy of type II muscle fibres. However, no patient had selective type I fibre atrophy. Enhanced enzymatic activity in single or multiple myofibrils was demonstrated by COX/SDH staining in approximately half of the specimens in group AII. In group AII, electron microscopy showed swelling, myelin figure denaturation of mitochondria, disruption of the myofibrils and increased lipid droplets in the gastrocnemius muscle. Increased concentration of LD was found in most specimens from group A patients. There were also reductions of SOD, NO, biochemical activity of Na+-K+-ATPase, Ca2+-ATPase with increasing concentration of LD in these patients, most prominently in group AII. We found correlation between AVP assessments and the biochemical measurements as well as morphological appearances of the gastrocnemius muscle. CONCLUSION: Venous hypertension results in pathophysiological changes in the gastrocnemius muscles of patients with DVI, associated with decreased calf pump function.

The value of MG7 antigen in predicting cancerous change in dysplastic gastric mucosa.

The aim of this study was to ascertain whether MG7Ag is a useful predictor of evolution of gastric dysplasia to carcinoma. A total of 1090 patients with confirmed dysplasia were stained immunohistochemically with MG7 monoclonal antibody by the ABC method. A prospective follow-up study was undertaken on 19 patients with MG7Ag positive staining and 16 with MG7 negative staining over a period of 10-78 months. The expression of MG7Ag was also compared in another two groups by conducting retrospective studies. One group showed an evolution into gastric cancer over 2-4 years, the other did not. Quantitative analysis of MG7Ag expression was carried out on the last two groups. The receiver operating characteristic curve and Youden index were used to assess the best critical value for MG7Ag. MG7Ag was found positive in 456/1090 cases (41.8%) with dysplasia. Prospective follow-up of 35 patients showed that 6/19 patients with MG7Ag positive staining developed gastric cancer, but there were no carcinomatous changes in 16 patients with MG7 negative staining. The results of MG7Ag expression in 72 cases with retrospective follow-up showed there were 24 with positive immunostaining among 34 cancerous cases (70.6%), and only 7 in 38 non-cancerous cases (18.4%) (p<0.01). Image analysis showed that an average MG7Ag density index ++0.19 could be regarded as the critical value for high risk of gastric mucosa with dysplasia evolving to cancer. Positive MG7Ag expression in gastric mucosa of patients with dysplasia, especially in cases with a density index ++0.19, was an indicator of high risk of malignant change.