The impact of age and number of mutations on the size of clonal hematopoiesis.

Clonal hematopoiesis (CH) represents the clonal expansion of hematopoietic stem cells and their progeny driven by somatic mutations. Accurate risk assessment of CH is critical for disease prevention and clinical decision-making. The size of CH has been showed to associate with higher disease risk, yet, factors influencing the size of CH are unknown. In addition, the characteristics of CH in long-lived individuals are not well documented. Here, we report an in-depth analysis of CH in longevous (≥90 y old) and common (60~89 y old) elderly groups. Utilizing targeted deep sequencing, we found that the development of CH is closely related to age and the expression of aging biomarkers. The longevous elderly group exhibited a significantly higher incidence of CH and significantly higher frequency of TET2 and ASXL1 mutations, suggesting that certain CH could be beneficial to prolong life. Intriguingly, the size of CH neither correlates significantly to age, in the range of 60 to 110 y old, nor to the expression of aging biomarkers. Instead, we identified a strong correlation between large CH size and the number of mutations per individual. These findings provide a risk assessment biomarker for CH and also suggest that the evolution of the CH is influenced by factor(s) in addition to age.

Ultrasound Biomicroscopy and High-Frequency Ultrasound for Evaluating Extramammary Paget Disease With Pathologic Correlation.

OBJECTIVES: The purpose of this study was to investigate the performance of ultrasound biomicroscopy (UBM) and high-frequency ultrasound (HFUS) in the assessment of extramammary Paget disease (EMPD) and to correlate the imaging features with pathologic findings. METHODS: In this retrospective study, we described the imaging features from UBM and HFUS based on 17 pathologically proven EMPD cases. The performance for visualizing layer involvement by UBM and HFUS was compared. Additionally, we checked the consistency between layer involvement of the lesions on UBM images and the pathologic results. Additionally, blood flow and the status of lymph nodes were investigated with HFUS. RESULTS: Ultrasound biomicroscopy revealed that all 17 lesions (100%) were hypoechoic and grew in a creeping form. The feature of layer involvement was shown in 10 lesions (58.8%) limited to the epidermis and 6 lesions (35.3%) involving the dermis, and the remaining lesion (5.9%) involved the full skin layers. Layer involvement was clearly displayed by UBM for all lesions (100%) but for only 5 lesions (29.4%) by HFUS (P < .001). Additionally, the layer involvement of 15 lesions (88.2%) on UBM was consistent with the pathologic results (κ = 0.746). High-frequency ultrasound revealed profuse blood flow in most lesions (64.7% [11 of 17]), and 1 case showed inguinal lymph node metastasis. CONCLUSIONS: Combined use of UBM and HFUS can provide key information on EMPD based on ultrasound features. Comparatively, UBM provides clearer morphologic information, whereas HFUS provides information on lymph node metastasis and blood flow.

[Effects of FBI-1 silencing on proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231].

This work aimed to observe the effects of short hairpin RNA (shRNA)-silenced FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) on proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231. qRT-PCR and Western blot analysis were applied to detect the mRNA and/or protein expression of FBI-1, Bcl-2, Bax, cleaved-Caspase 3 and Survivin. RNA interference method was used to silence FBI-1 expression in MDA-MB-231 cells. CCK-8 and colony formation assay were employed to detect the cell proliferation. Flow cytometry was employed for examining cell apoptosis. In vivo tumorigenicity of MDA-MB-231 cells was detected by tumor transplantation in nude mice. The results showed that the mRNA and protein expressions of FBI-1 were higher in MDA-MB-231 cells compared with those in normal human mammary epithelial cells MCF-10A. FBI-1 gene silencing inhibited proliferation and induced apoptosis of MDA-MB-231 cells in vitro, together with decreased Bcl-2 and Survivin protein expression, increased Bax protein expression and activated Caspase 3. Moreover, FBI-1 gene silencing inhibited the tumorigenesis of MDA-MB-231 cells in vivo. These results suggest that silencing of FBI-1 gene inhibits proliferation, induces apoptosis and suppresses the tumorigenesis of MDA-MB-231 cells.

[In vivo intestinal absorption characteristics of phloridzin in rats].

To study the in vivo intestinal absorption kinetics of phloridzin in rats. The absorption of phloridzin in the small intestines and colon of rats was investigated using an in vivo single-pass perfusion method and the drug concentration was measured by HPLC. The effects on intestinal absorption of different drug concentration and P-glycoprotein (P-gp) inhibitor were conducted. The results showed that the phloridzin could be absorbed in whole intestine, but more fully in the jejunum and colon segment,poorly absorbed in the duodenum and ileum. The absorption rate constant (Ka) and the apparent absorption coefficient（Papp）of phloridzin decreased following the sequence of jejunum> colon > duodenum > ileum. Absorption parameters of phloridzin had no significant difference at different concentration (5.14, 10.28, 20.56 mg•L⁻¹) . The saturate phenomena was not observed under the test range of drug concentration, and the absorption mechanism may be the passive diffusion transport.There had a significant difference in Ka and Papp values between P-gp inhibitor and no P-gp inhibitor groups. Phloridzin may be the substrate of P-gp.

[Optimization on Preparation of Total Saponins of Aralia taibaiensis Phospholipid Complex by Central Composite Design-Response Surface Method].

Objective: To optimize the preparation of total saponins of Aralia taibaiensis phospholipid complex( TSAT-PC) by the central composite design-response surface method. Methods: Total saponins of Aralia taibaiensis phospholipid complex was prepared by using solvent evaporation method, five factors including reaction solvent, reaction time, reaction temperature, ratio of reactants on this reaction, and the concentration of the drug were investigated, then to optimize the preparation of TSAT-PC by the central composite design response surface method, and to study its physicochemical properties. Results: The optimal process conditions were as follows, the reaction time was 1 h, the reaction temperature was 45 ℃,the ratio of soya lecithine ( SL) and TSAT was 3∶ 1, the reaction concentration was16 mg / m L, the complexing rate was 97. 23%,it was less than 5% with the predicted deviation; IR analysis proved the formation of TSAT-PC, and the solubility in the octyl alcohol was higher than the original drug. Conclusion: TSAT-PC was successfully developed by the optimized process, enhance the solubility in octyl alcohol, which provide the reference for the further development and utilization of Chinese materia medica preparation.

[Surveilance and response for Schistosomiasis japonica based on sentinel mice examination for cercariae-infested water in risk region, 2012].

OBJECTIVE: To monitor water body infestation in schistosomiasis high-risk areas with sentinel mouse technique. METHODS: A total of 72 surveillance sites from 47 counties were selected in Hunan, Hubei, Jiangxi, Anhui, Jiangsu, Yunnan, and Sichuan. The water infectivity of Schistosoma japonicum was determined in the surveillance sites by using sentinel mice during June-July and September, 2012. RESULTS: Among the 3,283 sentinel mice which were placed in 72 sites, 3,062 (93.3%) were recovered and dissected. Infected sentinel mice were found in six sites accounting for 8.3% (6/72) of the total surveillance sites, with an occurrence rate of sites with infected mice of 8.3% in June-July and 2.8% in September. 33 infected mice were discovered with a total infection rate of 1.08% (33/3,062). 1,085 adult worms were collected, with a mean worm burden of 32.9 worms per mouse in infected sentinel mice. 4 positive sites were in Hunan and 2 were in Jiangxi. Local acute schistosomiasis or suspected local acute cases which detected elsewhere were reported in 2 positive sites. Some follow-up activities were conducted in the 6 positive sites. CONCLUSION: Compared with those in 2010, the schistosomiasis risk areas are shrinking in 2012. However, some regions are still the schistosomiasis high-risk areas.

Multi-visceral resection of malignant tumors with left-sided portal hypertension.

BACKGROUND/AIMS: Left-sided portal hypertension (LSPH) is an uncommon clinical syndrome which may lead to bleeding from isolated gastric varices and pancreatitis is the most common etiology. Despite the particular rare incidence of LPSH caused by malignant tumor, the optimal management remains undefined. METHODOLOGY: From January 2006 to December 2009, a total of 8 patients of left-sided portal hypertension caused by malignancies were admitted into the department of surgery of our hospital. Medical records of those patients were retrieved and analyzed, including etiologies, clinical presentations, diagnostic methods and surgical approaches. RESULTS: Of current series, pancreatic tumors (5/8) and retroperitoneal tumors (3/8) were the primary etiologies. Those patients mainly presented with upper gastrointestinal bleeding or irregular left upper abdominal pain and isolated gastric varices became important clinical evidence. All those patients were performed multi-visceral resection. No recurrent upper gastrointestinal bleeding occurred during the follow-up period and three patients died 6, 18 and 21 months postoperatively. CONCLUSIONS: Although LSPH caused by malignant tumor is uncommon and difficult to deal with, deliberate evaluation of preoperative CT images will ensure the success of an aggressive multi-visceral resection and the prognoses in those patients are relatively promising.

Comparative study of thin sectional anatomical images from Chinese visible human data set and computed tomography images of superior mediastinum.

The structures of superior mediastinum and their spatial relationships are complex and difficult to master. This study aimed to compare visualization of the superior mediastinum based on computed tomography (CT) images and on the thin sections of the Chinese visible human (CVH) data set to provide a sectional anatomical basis for diagnostic imaging of superior mediastinal pathology. CVH sections of the mediastinum of a 35-year old male were compared with plain and enhanced CT images of a 45-year old male without apparent abnormalities in the upper chest. In addition, a three-dimensional model based on the CVH sections was compared with a model based on CT images. Although CT imaging is noninvasive and can be carried out in many individuals, its weakness is clearly the visualization of small soft tissue structures. In this respect, the sectional anatomical approach of the CVH images is complementary, as it visualizes these small soft tissue structures due to the higher resolution in the plain of sectioning and the color of the different structures in the section. Three-dimensional surface and volume rendering of reconstructions of the CVH data set can help medical students and less experienced thoracic surgeons to familiarize themselves with the topographic anatomy of the superior mediastinal structures and their spatial relationships, and thus with interpreting CT images of patients.

[Clinical analysis of 36 cases of esophageal mucoepidermoid carcinoma].

OBJECTIVE: To review the clinical characteristics, diagnosis, treatment and prognosis of esophageal mucoepidermoid carcinoma (MEC). METHODS: Clinical data of 36 patients with pathologically confirmed esophageal MEC who received surgical treatment in Cancer Hospital of Shantou University Medical College from Jan 1991 to Jun 2010 were retrospectively analyzed. The survival analysis was performed using Kaplan-Meier method. RESULTS: Of the 4253 patients diagnosed as esophageal cancer during the same time in our center, only 36 had esophageal MEC, accounted for 0.8%. This group included 27 men and 9 women ranging in age from 40 to 78 years (median 58 years). Esophageal MEC showed similar clinical symptoms, radiological and endoscopic features to esophageal squamous cell carcinoma (ESCC). Of the 20 cases who received preoperatively endoscopic biopsy, 18 were misdiagnosed as ESCC and 2 were misdiagnosed as esophageal adenosquamous carcinoma. The mean follow-up duration of this series was 38.8 months (3-142 months). 22 patients died of the disease during the follow-up period, 12 were still alive and 2 were lost of follow-up. The median survival time (MST) of the 36 patients was 29.0 months, and the 1-, 2-, 3-, and 5-year overall survival rates (OS) were 80.6%, 57.1%, 34.4%, 25.8%, respectively. CONCLUSIONS: Esophageal MEC is a rare disease and prone to be misdiagnosed by endoscopic biopsy. Surgical resection is the primary treatment but the prognosis is poor.

Liver transplantation as a treatment for complicated bile duct injury.

BACKGROUND/AIMS: Bile duct injury during cholecystectomy can be successfully managed by biliary reconstruction in the majority of patients. However it can also lead to potentially severe complications with unpredictable long-term results and in fact a proportion of these cases may even require liver transplantation. METHODOLOGY: In recent years, two cases of complicated bile duct injury after the failure of traditional surgical interventions were admitted to our hospital. Both patients underwent liver transplantation successfully, and the detailed clinical data was analyzed retrospectively. RESULTS: Bile duct injury (Strasberg type E4) in one patient was caused by laparoscopic cholecystectomy associated with proper hepatic artery injury; after the failure of an initial Roux-en-Y hepaticojejunostomy, the patient underwent classical orthotopic liver transplantation. Bile duct injury (Strasberg type D) in the other patient was caused by abdominal trauma in his childhood. After several unsuccessful surgical interventions, the patient finally developed secondary biliary cirrhosis twelve years later. He therefore underwent a living related liver transplantation. The outcome of both patients was satisfactory. CONCLUSIONS: Liver transplantation should be considered when bile duct injury has occurs concomitant with severe vascular injury or secondary biliary cirrhosis appears after failure of surgical intervention.

Improving the diagnosis of AUS/FLUS thyroid nodules using an algorithm with combination of BRAFV600E mutation analysis and ultrasound pattern-based risk stratification.

PURPOSE: To propose a diagnostic algorithm for improving the diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) thyroid nodules. METHODS: This study retrospectively enrolled 77 consecutive patients with 81 AUS/FLUS nodules who underwent preoperative BRAFV600E mutation analysis. A new diagnostic algorithm was proposed that BRAFV600E mutation analysis for the Fine-needle aspiration cytology specimen was firstly carried out, in which positive BRAFV600E mutation indicated malignancy and classification of the nodules with negative BRAFV600E mutation was further performed based on ultrasound pattern-based risk stratification of American Thyroid Association Guidelines. The diagnostic performance of the new diagnostic algorithm was evaluated. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the receiver operating characteristic curve (AUROC) of new diagnostic algorithm were 94.6%, 84.0%, 91.4%, 86.9%, 90.1%, and 0.893, respectively. The proposed diagnostic algorithm significantly increased the diagnostic performances (AUROC: 0.893 vs. 0.837 and 0.795), sensitivity (94.6% vs. 71.4% and 75.0%), and accuracy (90.1% vs. 79.0% and 77.8%) compared with BRAFV600E mutation analysis alone and ultrasound pattern-based risk stratification alone (all P < 0.05). CONCLUSION: The proposed diagnostic algorithm is helpful for improving the diagnosis of AUS/FLUS nodules, which might be as a routine approach.

Resveratrol Mediates the Apoptosis of Triple Negative Breast Cancer Cells by Reducing POLD1 Expression.

Resveratrol (RSV) is known to possess anticancer properties in many types of cancers like breast cancer, in which POLD1 may serve as a potential target. However, the anticancer mechanism of RSV on triple negative breast cancer (TNBC) remains unclear. In the present study, the antitumor effects and mechanism of RSV on TNBC cells were analyzed by RNA sequencing (RNA-seq), which was then verified via cell counting kit-8 (CCK8), immunofluorescence, immunohistochemistry, Western Blot (WB), flow cytometry, and hematoxylin-eosin (HE) staining. According to the corresponding findings, the survival rate of MDA-MB-231 cells gradually decreased as RSV treatment concentration increased. The RNA-seq analysis results demonstrated that genes affected by RSV treatment were mainly involved in apoptosis and the p53 signaling pathway. Moreover, apoptosis of MDA-MB-231 cells induced by RSV was observed to be mainly mediated by POLD1. When treated with RSV, the expression levels of full length PARP1, PCNA, and BCL-2 were found to be significantly reduced, and the expression level of Cleaved-PARP1 as well as Cleaved-Caspase3 increased significantly. Additionally, the mRNA expression of POLD1 was significantly reduced after treatment with RSV, and the protein expression level was also inhibited by RSV in a concentration-dependent manner. The prediction of domain interaction suggested that RSV may bind to at least five functional domains of the POLD1 protein (6s1m, 6s1n, 6s1o, 6tny and 6tnz). Furthermore, after RSV treatment, the anti-apoptotic index (PCNA, BCL-2) of MDA-MB-231 cells was found to decrease while the apoptosis index (caspase3) increased. Moreover, the overexpression of POLD1 reduced the extent of apoptosis observed in MDA-MB-231 cells following RSV treatment. Moreover, animal experimental results showed that RSV had a significant inhibitory effect on the growth of live tumors, while POLD1 overexpression was shown to antagonize this inhibitory effect. Accordingly, this study's findings reveal that RSV may promote the apoptosis of TNBC cells by reducing the expression of POLD1 to activate the apoptotic pathway, which may serve as a potential therapy for the treatment of TNBC.

[Horticultural plant diseases multispectral classification using combined classified methods].

The research on multispectral data disposal is getting more and more attention with the development of multispectral technique, capturing data ability and application of multispectral technique in agriculture practice. In the present paper, a cultivated plant cucumber' familiar disease (Trichothecium roseum, Sphaerotheca fuliginea, Cladosporium cucumerinum, Corynespora cassiicola, Pseudoperonospora cubensis) is the research objects. The cucumber leaves multispectral images of 14 visible light channels, near infrared channel and panchromatic channel were captured using narrow-band multispectral imaging system under standard observation and illumination environment, and 210 multispectral data samples which are the 16 bands spectral reflectance of different cucumber disease were obtained. The 210 samples were classified by distance, relativity and BP neural network to discuss effective combination of classified methods for making a diagnosis. The result shows that the classified effective combination of distance and BP neural network classified methods has superior performance than each method, and the advantage of each method is fully used. And the flow of recognizing horticultural plant diseases using combined classified methods is presented.

[A variation of the recurrent laryngeal nerve at its entry to larynx found in the thyroid surgery].

OBJECTIVE: To describe a new variation of the recurrent laryngeal nerve (RLN) at its entry to larynx. METHODS: A retrospective study including 3 078 consecutive cases received thyroidectomy was performed from January 1998 to December 2008. The age ranged from 15 to 82 years, 2 395 cases were female and 683 cases were male. A total of 4 241 RLNs were exposed successfully for avoiding the injury of the nerve. A kind of variation of the RLN was reported in this study. RESULTS: Forty-four varied RLNs were identified at the entry into the larynx (1.0%, 44/4241). Variation happened at the truck or the branches of RLN entering the larynx far from the posterior cricothyroid joints. The distance from the entry to the back of cricothyroid joints was over 5 mm. Among these, eight RLNs (23.5%, 8/34) walked distally from the dorsal cricothyroid joint without extra laryngeal branches and entered the larynx at the abnormal point. There were four different kinds of sub-variations identified: type I: there was no branch in RLN and the varied RLN entered the larynx far from the posterior cricothyroid joints, total 35 cases (79.6%, 35/44); type II: there were two branches in RLN, one branch entered the larynx at the posterior cricothyroid joints and the other far from the posterior cricothyroid joints, total 5 cases (11.4%, 5/44); type III: there were two branches in RLN, and both branches entered the larynx far from the posterior cricothyroid joints, total 3 cases (6.8%, 3/44); type IV: there were three branches in RLN, the lateral branch of the varied RLN entered the larynx far from the posterior cricothyroid joints, total 1 case (2.2%, 1/44). Four varied RLNs were injured during the operation (9.1%, 4/44). CONCLUSION: The variation of RLN reported in this study is more dangerous and should be paid more attention to lower the injury of the nerve.

[Efficacy and adverse effects of film coated praziquantel for treatment of schistosomiasis japonica].

OBJECTIVE: To understand the adverse and curative effects of film coated praziquantel for treatment of schistosomiasis japonica. METHODS: A questionnaire survey was conducted among 6 to 65 years old inhabitants from epidemic areas of schistosomiasis japonica in Jiangxi, Anhui and Hubei provinces, while indirect haemagglutination assay (IHA) was also administrated. The Serological positives were tested by Kato-Katz technique. A total of 509 habitats of serological positives and healthy persons were given praziquantel. 460 targets with no relative symptoms were followed up for adverse effect of drugs in one month and efficacy evaluation of praziquantel was carried out in 104 parasitological positives 3 months post-treatment. RESULTS: The 84.7% (144/170) individuals thought film coated tablets were no smell or only with little smell while 92.9%(315/339) targets in control group fell that tablets smelled bad. The total side effect rates of film coated praziquantel group and control group in 1-2 hours post-treatment were 20.30% (27/133) and 83.18% (272/327) respectively. There was significantly different between two groups (chi(2) = 164.316, P < 0.05). The adverse effect rates of film coated praziquantel group in neuromuscular system, digestive system and cardiovascular system were 15.79% (21/133), 9.77% (13/133), 2.26% (3/133) individually which were significantly lower than those of control groups with 81.65% (267/327), 49.24% (161/327), 12.84% (42/327) in corresponding systems (chi(2)(neuromuscular system) = 175.188, chi(2)(digestive system) = 62.601, chi(2)(cardiovascular system) = 12.010, P < 0.05). And the adverse effect rate of allergic reaction of film coated group was no significant difference with control group (2.26%(3/133) versus 0.92% (3/327), chi(2) = 1.315, P = 0.235). One day after treatment, the adverse effect rate of film coated tablets of praziquantel decreased to 3.01% (4/133), significantly lower than that of control group (P < 0.05). There was no significant difference after 2 weeks treatment while the adverse effect rates decreased to 0.75%(1/133), 0.61% (2/327) in film coated praziquantel group and control group respectively (chi(2) = 0.029, P = 0.642). The curative rates 3 months post treatment were 84.91% (45/51) in film coated tablets of praziquantel group and 82.35% (42/53) in control group without significant difference (chi(2) = 1.536, P = 0.215). CONCLUSION: The smell and adverse effects of film coated tablets of praziquantel were decreased significantly and its efficacy for treatment of schistosomiasis japonica was equal to the control tablets. The film coated tablets of praziquantel might be applied in field widely after a further verification.

[The retrospective analysis of surgical outcome of portal hypertension].

OBJECTIVE: To retrospectively analyze the surgical outcome of portal hypertension and explore the risk-factors of long-term survival after operation. METHODS: The data of 149 patients (male 119, female 30, aged from 19 to 73 years old) with portal hypertension treated surgically from January 1996 to October 2007 was collected. Among these patients, there were 110 patients for Child A and 39 patients for Child B according to Child-Pugh classification. According to different surgical modality, all patients were divided into devascularization group (n = 85) and shunting group (n = 64). RESULTS: The follow-up rate was 78.8% and the average follow-up time was (46.3 +/- 30.4) months. The overall survival rates of 1-, 3-, 5- and 10-years were 95.6%, 88.7%, 83.4% and 65.1% respectively. Meanwhile the survival rates of 1-, 3-, 5- and 10-years in devascularization group and in shunting group were 95.4%, 87.7%, 80.6%, 56.3% and 95.8%, 90.1%, 86.8%, 72.6% respectively. There was no significant difference in survival rate between these two groups (P > 0.05). Child-Pugh classification has been the most important risk-factor that could influence long-term survival after operation by analysis of COX regression and it showed that the long-term survival time in Child A was longer than in Child B. The re-hemorrhage rates of 1-, 3- and 5-years in shunting group would be much better than in devascularization group. The rate of postoperative encephalopathy in devascularization group and shunting group was 6.9% and 6.1% respectively and there was no significant difference (P > 0.05). The portal venous pressure and flow of portal vein decreased significantly after shunting operation (P < 0.05). CONCLUSIONS: The mainly sole risk-factor of long-term survival for portal hypertension has been the classification of Child-Pugh, not surgical procedure. The individualized proximal splenorenal shunt is much better than devascularization in controlling variceal hemorrhage.

G59S mutation in the GJB2 gene in a Chinese family with classic Vohwinkel syndrome.

Vohwinkel syndrome (VS) is a rare autosomal dominant condition, also known as mutilating palmoplantar keratoderma accompanied by sensorineural deafness. The LOR and GJB2 genes are reported to be responsible for VS. The GJB2 gene encodes connexin 26, a component of intercellular gap junctions expressed in various tissues. We report the case of a 31-year-old Chinese woman with classic VS characterized by sensorineural deafness and mutilating palmoplantar keratoderma. Further genetic studies demonstrated a nucleotide change (c.175G>A) in the GJB2 gene, leading to an amino acid alteration (G59S). This identical missense mutation (G59S) has also been reported in a patient with Bart-Pumphrey syndrome. Together with our findings and previous studies, we conclude that the identical mutation (G59S) in the GJB2 gene contributes to various manifestations.

The impact of mitochondrial energetic dysfunction on apoptosis in outer hair cells of the cochlea following exposure to intense noise.

Previous studies have shown that exposure to intense noise causes outer hair cells (OHCs) to die, primarily through the process of apoptotic degeneration. The current study was designed to examine the regulatory role of mitochondrial bioenergetic function in controlling the initiation and execution of the apoptotic process of OHCs. Chinchilla cochleae were treated with 3-nitropropionic acid (3-NP, 20 or 50mM), an irreversible inhibitor of succinate dehydrogenase (SDH), to inhibit the mitochondrial energy production before and after exposure to 75 pairs of impulses at 155dB pSPL. Comparison of the noise-exposed cochleae treated with and without 3-NP revealed that the inhibition of SDH activity delayed nuclear degradation in apoptotic OHCs. However, the initiation of apoptosis appeared to be undeterred. There was no major shift of cell death pathways from apoptosis to necrosis, although a small portion of OHCs showed signs of secondary necrosis. Collectively, the results of the study suggest that, while the mitochondrial energetic function plays an important role in regulating the apoptotic process, its dysfunction has a limited influence on the suppression of apoptotic induction in OHCs following exposure to intense noise.

Apoptotic outer hair cell death in the cochleae of aging Fischer 344/NHsd rats.

Apoptotic cell death has been implicated in cochlear degeneration during aging. To better understand the impact and the biological process of outer hair cell (OHC) apoptosis, we investigated the contribution of apoptotic cell death to the formation of the OHC lesions, and observed the temporal patterns of the occurrence of apoptotic events associated with the mitochondrial pathway in Fischer 344/NHsd rats, with ages ranging from 20 to 27 months. The results showed that the ratio of apoptotic to necrotic OHCs was 8:1. During the process of cell degeneration, the onset of Bax expression, cytochrome c release, and nuclear DNA fragmentation preceded the onset of nuclear condensation. In contrast, the activation of caspases-3 and -9, as well as the degradation of F-actin, took place after the onset of nuclear condensation. The results of this study suggest that the initiation of nuclear degradation is a caspase-3-independent process. Moreover, the study revealed that OHCs with Bax expression or cytochrome c release could enter either the apoptotic or necrotic pathway, suggesting the presence of a regulatory mechanism that guides degenerating OHCs to die via either the apoptotic or necrotic pathway.

[A clinical study on splanchnic hemodynamic changes after orthotopic liver transplantation for patients with portal hypertension].

OBJECTIVE: To study the regularity of splanchnic hemodynamic changes after orthotopic liver transplantation (OLT) for patients with portal hypertension. At the same time, effect of such changes on splenomegaly, hypersplenism, collateral circulation and the postoperative liver function was discussed. METHODS: Between June 2002 and October 2005, 173 liver transplantations were performed. In 38 patients with portal hypertension undergoing OLT, the following parameters were measured before surgery and subsequently at 1, 3, 5, 7 days, 1, 6 months and 1, 2, 3 years after operation by using Color Doppler sonography: portal blood flow mean velocity (PBV), portal blood flow volume (PBF), hepatic artery resistance indexes (HA-RI) and spleen size. The same parameters were measured in 8 patients with acute liver failure and 20 healthy controls. Meanwhile to observe liver function and varicose vein of esophagus. RESULTS: In cirrhotics, PBV and PBF increased immediately after transplantation [from (13.7 +/- 4.2) cm/s to (58.4 +/- 25.2) cm/s and from (958 +/- 445) ml/min to (3024 +/- 1207) ml/min respectively, P < 0.05]. HA-RI also augmented [from (0.65 +/- 0.11) to (0.74 +/- 0.12), P < 0.05]. PBV returned to normal values after 6 months, PBF returned to normal value after 2 years. Spleen size decreased significantly, but splenomegaly persisted after 3 years. In addition the esophagogastric varix ameliorated significantly. CONCLUSIONS: Abnormal splanchnic hemodynamic changes for patients with portal hypertension still will long-term exist after OLT, but does not effect recovery of hypersplenism, esophagogastric varix and liver function.