The 100 most-cited articles in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD), the second most common neurodegenerative disease, has serious clinical effects. Research on PD is increasing, but the quantity and quality of this research have not been reported. METHODS: To analyze the most-cited articles on PD and provide information about developments in this field, we searched for articles in the Web of Science for the keyword "Parkinson*" in the title. We selected the 100 most-cited articles and evaluated information including citation number, publication time, journal, impact factor, authors, original country, institution of corresponding author, and study type. RESULTS: Citation numbers for the 100 most-cited articles ranged from 669 to 6902, with a median of 944. The 100 articles were published from 1967 to 2009, with most appearing between 1996 and 2000 (n = 24) and 2001 to 2005 (n = 27). The publications appeared in a total of 31 journals, led by Science with 15 and the New England Journal of Medicine (NEJM) with 13. The majority (84%) of the 100 most-cited articles had ≥ 3 authors. The articles originated from 14 countries, led by the USA (n = 44) and England (n = 17). Among the 100 most-cited articles, 24 were clinical studies, 54 were laboratory studies, 20 were reviews, and 2 were clinical guidelines. None of these articles originated from South America, Oceania, or Africa. CONCLUSIONS: The present study provides historical perspectives on the progress of PD research and highlights trends and academic achievements in this field.

Idiopathic hypertrophic spinal pachymeningitis: a case report and review of literature.

PURPOSE: To report an unusual case of idiopathic hypertrophic spinal pachymeningitis (IHSP) with a review of relevant literature and to discuss the etiology, clinical features, imaging, treatment and prognosis of IHSP. METHODS: The case of a 44-year-old woman is reported. MEDLINE was used to search relevant literatures written in English since 2004. RESULTS: The patient suffered from progressive mild thoracic backache followed by truncal and lower extremity weakness, numbness and urinary retention. The diagnosis was confirmed by magnetic resonance (MR) imaging and histopathologic examination. Although she received corticosteroid therapy and decompressive surgery, the patient suffered a rapid relapse probably because of the withdrawal of postoperative steroid therapy. CONCLUSIONS: IHSP is a rare disease characterized by inflammatory hypertrophy of the dura mater without identifiable cause and featured clinical progress of radiculalgia to myelopathy. It is a diagnosis of exclusion. In our view, surgical decompression with postoperative steroid therapy may be optimal. Furthermore,we speculated that increased levels of protein and cell count in cerebrospinal fluid (CSF) might be positively related to the disease progression. High inflammatory signs or CSF protein and cell levels before surgery or postoperative residual lesions are possible reasons of poor prognosis in patients with IHSP.

Hepatocellular carcinoma recurrence is an independent risk factor for HB recurrence after liver transplantation.

BACKGROUND/AIMS: To confirm the relationship between hepatitis B recurrence and Hepatocellular carcinoma recurrence. METHODOLOGY: Data from 340 patients undergoing liver transplantation for HBV-related liver disease were retrospectively evaluated. Clinically relevant variables were analyzed using univariate models. Significant variables were subjected to multivariate logistic regression analysis to identify the independent predictors for HBV recurrence. Fifteen samples removed from HCC recurrence patients were stained for HBsAg and HBcAg. RESULTS: The analyzed population included 283 male and 57 female patients. The mean age was 48.5±9.33 years and median follow-up was 47 months. Hepatitis B relapsed in 16 patients (4.7%). Univariate analysis indicated that HCC (P=0.022) and HCC recurrence (P=0.000) were associated to post transplantation HB. Multivariate analysis identified HCC recurrence as an independent risk factor for HB recurrence (hazard ratio: 23.262 (95% CI: 3.752, 144.216); P <0.001). Three of 15 metastatic lesions were positive for HBsAg and 1 lesion was positive for HBcAg. Conclusion: HCC recurrence is an independent risk factor for post transplantation recurrence of hepatitis.

The Golgi Apparatus: Panel Point of Cytosolic Ca(2+) Regulation.

The Golgi apparatus (GA), an intermediate organelle of the cell inner membrane system, plays a key role in protein glycosylation and secretion. In recent years, this organelle has been found to act as a vital intracellular Ca(2+) store because different Ca (2+) regulators, such as the inositol-1,4,5-triphosphate receptor, sarco/endoplasmic reticulum Ca(2+) -ATPase and secretory pathway Ca 2+ -ATPase, were demonstrated to localize on their membrane. The mechanisms involved in Ca(2+) release and uptake in the GA have now been established.Here, based on careful backward looking on compartments and patterns in GA Ca (2+) regulation, we review neurological diseases related to GA calcium remodeling and propose a modified cytosolic Ca(2+) adjustment model, in which GA acts as part of the panel point.

[Effects of low-dose chlorpyrifos exposure on dopaminergic neurons in the midbrain substantia nigra and neural behavioral development in neonatal rats].

OBJECTIVE: To explore the effects of low-dose chlorpyrifos (CPF) exposure on dopaminergic (DA) neurons in the midbrain substantia nigra and neural behavioral development in neonatal rats. METHODS: Postnatal 11 day old Sprague-Dawley rats were randomly assigned into CPF, menstruum dimethysulfoxide (DMSO) and normal saline (NS) groups. The rats in the CPF group were injected with low-dose CPF (5 mg/kg?d) on postnatal days 11-14. The two control groups were injected with DMSO or NS respectively. The rats were sacrificed on postnatal days 15, 20, 30, and 60. Body weight gain, outward appearance of brain tissue, the coefficient of brain and the water content of brain tissue were measured. Tyrosine hydroxylase (TH) expression in DA neurons in the midbrain substantial nigra was examined by immunohistochemical straining. Immune electron microscopy was used to examine the subcellular structure of DA neurons. Open field test, grip strength test, slope test and Morris water maze test were used to examine the neurobehavioral changes. RESULTS: The outward appearance of brain tissue was normal in the three groups. There were no significant differences in the absolute value of body weight gain, the coefficient of brain and the water content of brain tissue among the three groups. CPF exposure decreased the level of TH immunoreactivity (P<0.05) in the substantia nigra of CPF group since postnatal day 30 compared with the DMSO and NS groups. The subcellular structures of some DA neurons in the CPF group were impaired. Decreased motor activity and learning and memory impairments were observed in the CPF group compared with those in the DMSO and NS groups (P<0.05) since postnatal day 30. CONCLUSIONS: CPF exposure during the neonatal period can cause long-term motor activity and learning and memory impairments in accompany with DA neurons damage in the midbrain substantia nigra.

Effect Evaluation of Strychnos nux-vomica L. with Integrative Methods for Bortezomib-Induced Peripheral Neuropathy in Multiple Myeloma Patients: A Self-Controlled Clinical Trial.

OBJECTIVE: To explore the clinical effect and adverse reactions of Strychnos nux-vomica in bortezomib-induced peripheral neuropathy (BIPN) of patients with multiple myeloma (MM). METHODS: A total of 19 MM patients with BIPN were enrolled and Nux Vomica Capsule (NVC, 0.4 g, thrice daily) were orally administrated for 30 days. Comparative analysis on parameters between pre- and post-therapy, including peripheral neuropathy (PN) grade, neurotoxicity score, Chinese medicine (CM) syndrome score, total neuropathy score (TNS), coagulation function, and serum nerve growth factor (NGF) levels were conducted. The adverse events were monitored. RESULTS: In BIPN of MM patients who received NVC, PN grade was lowered, neurotoxicity score was obviously decreased (P⩽0.01), and both CM syndrome score and TNS were remarkably decreased (P<0.01). After the therapy, activated partial thromboplastin time was prolonged (P<0.01) and fibrinogen was declined (P<0.05), showing improvement in the hypercoagulable state of patients. No significant difference of NGF recovery degrees was detected between pre- and post-therapy (P>0.05). No evident adverse reactions were observed during the course of treatment. CONCLUSION: Strychnos nux-vomica L. has significantly effect with a good safety in treatment of BIPN in MM patients.

[Association of single nucleotide polymorphisms of kallikrein 1 gene with cerebral hemorrhage in Changsha Han Chinese].

OBJECTIVE: To explore the association between single nucleotide polymorphisms (SNPs) of KLK1 gene and cerebral hemorrhage in Changsha Han Chinese. METHODS: Two hundred and seventy-three cerebral hemorrhage (CH) patients and 140 healthy controls were collected. The SNPs of rs5516 and rs5517 loci of KLK1 gene were analyzed by SNaPshot methods and direct sequencing. RESULTS: (1)Genotype and allele frequencies in rs5516 locus had no difference between the CH patients and controls (P> 0.05). However, the A allele frequency of the rs5517 locus in CH patients was higher than that in the control group (0.419, 0.321 respectively, P< 0.05). (2)In the control group,the levels of diastolic blood pressure (DBP) of the GA and AA genotype carriers of the rs5517 locus were significantly higher than those of the GG genotype (P< 0.05), while the levels of blood pressure were not significantly different among different genotypes of the rs5516 polymorphism in both CH patients and the control group(P> 0.05). CONCLUSION: Author's preliminary results suggested that the rs5517 polymorphism was associated with cerebral hemorrhage, while the rs5516 polymorphism was not in Changsha Han Chinese.

[Effect of hyperprolactinemia upon clinical symptoms of patients with polycystic ovary syndrome].

OBJECTIVE: To determine the effects of hyperprolactinemia (hyperPRL) upon the symptoms of patients with polycystic ovary syndrome (PCOS). METHODS: Age, body mass index, levels of hormone, lipid, beta-cell function and family medical history of 224 women with PCOS and 30 women with hyperPRL + PCOS were compared. RESULTS: Patients with hyperPRL + PCOS were younger to develop endocrine disturbances, an increased incidence of acne (64% vs 28% respectively), a high level of androstenedione (20 + or - 7 vs 13 + or - 5) nmol/L respectively and prolactine in serum (1492 + or - 1175 vs 367 + or - 164) mIU/L respectively; The PCOS patients were divided into the groups of hyperandrogenism PCOS and non-hyperandrogenism PCOS depending on the serum level of androgen. A higher level of T and A was found in serum in PRL-PCOS than non-hyperandrogenism patients and similar as hyperandrogenism PCOS patients. They had reduced ApoB (680 + or - 230 nmol/L vs 943 + or - 179 mmol/L respectively) and Lpa level (46 + or - 22 nmol/L vs 162 + or - 194 mmol/L respectively) and high HOMA-IR when compared with non-hyperandrogenism PCOS; Patients' sisters with hyperPRL + PCOS had a significantly greater incidence of acne, higher rates of infertility and PCOS when compared with PCOS patients. Levels of other hormones, metabolic profiles and other family histories did not differ between patients with PCOS and hyper-PRL+PCOS. CONCLUSION: Patients with hyperPRL + PCOS develop the endocrine disturbances at a younger age, a greater incidence rate of acne, level of prolactin and androstenedione, they have reduced ApoB and increased HOMA-IR. Patients' sisters with hyperPRL + PCOS have significantly greater incidence of acne, higher rates of infertility and PCOS as when compared with PCOS patients.

[Effect of zengjing no. 1 capsule on morphology and motility of sperm in patients with oligospermia].

OBJECTIVE: To explore the effect of Zengjing Capsule No. 1 (ZJC1) on morphology and motility of sperm in patients with oligospermia (OSM). METHODS: Seventy-two OSM patients were assigned to 2 groups by a randomizing digital table, the treated group and the control group, they were treated respectively by ZJC1 and Wuzi Yanzong Pill (WYP). The changes of density, motility and morphology of sperm in patients before and after 3-month treatment were examined using computerized WLJY-9000 colour semen analysis system with refined Papanicolaou's stain. RESULTS: The density, motility and morphology of sperm were improved and sperm deformity rate was significantly decreased after treatment in both groups (P < 0.01), but the effects in the treated group were better than those in the control group (P < 0.01). CONCLUSION: ZJC1 can enhance the density and motility of sperm and reduce the sperm deformity rate in patients with OSM.

Electroacupuncture effects in a rat model of complete Freund's adjuvant-induced inflammatory pain: antinociceptive effects enhanced and tolerance development accelerated.

We have previously shown that electroacupuncture (EA) produced antinociception through the release of endogenous opioid peptides to activate opioid receptors during acute nociception. EA produced tolerance after its prolonged application. It has reported that 100 Hz EA could reduce mechanical hyperalgesia in complete Freund's adjuvant (CFA)-induced inflammatory nociception rats. The present study aims to investigate the antinociceptive effect of EA and the development of EA tolerance in chronic inflammatory nociception rats with CFA injection into the hind paw plantar. The results showed that the antinociceptive effect of 100 Hz EA was significantly enhanced in CFA-induced inflammatory nociception rats. Naloxone at 20 mg/kg could significantly block this antinociceptive effect. Chronic tolerance to EA was developed faster in CFA-induced inflammatory nociception rats than in normal rats. Therefore, 100 Hz EA could enhance antinociceptive effects and accelerate tolerance development in CFA-induced inflammatory nociception rats. The enhancement of EA antinociceptive effect in CFA-induced inflammatory nociception rats might involve the endogenous opioid peptides such as dynorphin.

Expression of PD-1 on CD4+ Tumor-Infiltrating Lymphocytes in Tumor Microenvironment Associated with Pathological Characteristics of Breast Cancer.

OBJECTIVE: This study aimed to investigate the correlation of CD4+/PD-1+ or CD4+/PD-1- tumor-infiltrating lymphocytes with pathological characteristics in breast cancer patients. METHODS: A cross-sectional study consecutively recruited 133 patients with invasive ductal breast cancer. The expression of CD4, programmed cell death protein 1 (PD-1), CK7, CK20, E-cadherin, or Ki-67 was detected by immunohistochemistry. The associations between CD4+/PD-1+ or CD4+/PD-1- tumor-infiltrating lymphocytes and pathological characteristics were evaluated. RESULTS: Elderly patients intended to have a lower level of CD4+/PD-1- tumor-infiltrating lymphocytes (p < 0.05). Patients with positive E-cadherin expression had higher median cell counts of CD4+/PD-1- tumor-infiltrating lymphocytes than patients with negative E-cadherin expression (30/HPF versus 10/HPF, p < 0.05). Counts of CD4+/PD-1+ tumor-infiltrating lymphocytes had a significant correlation with Ki-67 index that the correlation coefficient was 0.29 (p = 0.001). Positive CK20 expression was related to a higher level of CD4+/PD-1- tumor-infiltrating lymphocytes than negative CK20 expression (73/HPF versus 30/HPF, p < 0.05). CONCLUSION: CD4+/PD-1+ or CD4+/PD-1- tumor-infiltrating lymphocytes showed diverse association with pathological features of breast cancer. CD4+/PD-1+ tumor-infiltrating lymphocytes had a significant relationship with Ki-67 expression whereas CD4+/PD-1- tumor-infiltrating lymphocytes had a significant relationship with E-cadherin expression. Further studies are warranted to explore the immunomodulatory effects of phenotypes of CD4+ T cell subsets in breast cancer.

CCK(B) receptor antagonist L365,260 potentiates the efficacy to and reverses chronic tolerance to electroacupuncture-induced analgesia in mice.

Cholecystokinin octapeptide (CCK-8) is a physiological antagonist of endogenous opioids in the central nervous system (CNS). Our previous work has shown that CCK-8 plays an important role in the development of tolerance to morphine analgesia and electroacupuncture (EA) analgesia in the rat. The present studies were designed to examine whether the CCK(B) receptor is involved in the modulation of EA analgesia and the development of EA tolerance in mice. The latency to flick the tail in the radiant heat was used as index to assess the efficacy of EA analgesia. Subcutaneous (s.c.) injection of the CCK(B) receptor antagonist L365,260 produced a dose-dependent (0.125-2.0 mg/kg) potentiation of the analgesia induced by 100 Hz EA, with a maximal effect occurred at 0.5 mg/kg. In addition, L365,260 (0.5 mg/kg) significantly reversed chronic tolerance to 100 Hz EA in mice. These results suggest that the CCK(B) receptor might play a role in the tonic inhibition of 100 Hz EA-induced analgesia and in the mediation of chronic tolerance to 100 Hz EA in mice. The results opened a way for further investigation of the function of CCK-8 in pain modulation using inbred strains of mice.

Liver transplantation in adults with portal vein thrombosis: Data from the China Liver Transplant Registry.

OBJECTIVES: Portal vein thrombosis (PVT) is a common complication in patients with liver cirrhosis. During liver transplantation (LT), PVT may complicate the procedure and lead to a poor prognosis. The aim of this study is to evaluate patients enrolled in the China Liver Transplant Registry, to understand the influence of PVT to the LT recipients. METHODS: We collected data from patients who underwent LT and were entered into the China Liver Transplant Registry. All data of medical records and follow-up were retrospectively reviewed. The preoperative condition, duration of surgery, intraoperative blood loss, postoperative early and late PVT, and survival rates were compared between patients with PVT and those without PVT. Multivariate Cox analysis and survival analysis were used to determine the influence of PVT. RESULTS: A total of 20,524 cases were recruited into the study. In all, 1810 (8.82%) patients were diagnosed with preoperative PVT of various severities. All patients were followed up for an average of 30.25±33.25months (up to a maximum of 171.68months). Patients with PVT had a significantly longer operating time, more intraoperative blood loss and a higher rate of post-LT PVT (P<0.001). Multivariate Cox analysis showed that PVT did not reduce the recipients' survival rate (HR=0.89, 95% CI: 0.774-1.024, P=0.103). There was no significant difference in cumulative survival rate (P=0.059) between patients without PVT, and patients with PVT. CONCLUSIONS: PVT increases the difficulty of LT, but doesn't reduce the survival rate. Therefore, PVT is not an absolute contraindication for LT in experienced transplantation centers.

Quality of Life in Patients After Maxillectomy and Placement of Prosthetic Obturator.

PURPOSE: The aim of this study was to assess quality of life (QoL) and obturator functioning in patients having undergone a maxillectomy as a tumor ablative resection and rehabilitation with a prosthetic obturator. MATERIALS AND METHODS: The University of Washington Quality of Life scale version 4 (UW-QoLv4) and the Obturator Functioning Scale (OFS) were used to evaluate the self-reported QoL and obturator functioning. The effects of demographic and treatment variables on QoL were assessed using age, defect size, postoperative radiotherapy (RT), neck dissection, and dentition. RESULTS: The study included 16 men and 13 women with a mean age of 48.8 years. Of the 29 patients, 16 had a Brown Class 2a or smaller defect and 13 had a Brown Class 2b or larger defect. The mean OFS score (P = .004) and the physical (P = .001) and social-emotional function scores (P = .001) of the patients who received postoperative RT were significantly lower than those who did not receive postoperative RT. The subscales for swallowing (P = .008), saliva (P = .001), pain (P = .001), and shoulder function (P = .002) correlated strongly with postoperative RT on the UW-QoL. The subscales for pronunciation (P = .007) and saliva (P = .002) correlated significantly with RT on the OFS. The mean OFS scores were significantly lower for the patients with a Brown Class 2a or smaller defect than for Brown Class 2b or larger (P = .005). CONCLUSION: Postoperative RT was the strongest variable affecting QoL in patients with maxillectomy and prosthetic obturator reconstruction. The size of the defect slightly influenced the obturator function; however, it did not influence the overall QoL.

[Effects of atorvastatin on plasma hypersensitive C-reactive protein and interleukin-6 in patients with acute cerebral infarction].

OBJECTIVE: To observe the effects of different doses of atorvastatin on the plasma hypersensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with acute cerebral infarction. METHODS: 131 patients with acute cerebral infarction, 73 males and 58 females, aged 63 +/- 11, were randomly divided into 3 groups: Group A (n = 47), with basal treatment; Group B (n = 42), atorvastatin 10 mg was added every night; and Group C (n = 42), atorvastatin 20 mg was added every night. Before the treatment and 7 and 14 days after the treatment the plasma levels of hsCRP and IL-6, fasting plasma levels of lipid, such as total cholesterol (TC) and low density lipoprotein-C (LDL-C), liver functions, such as aspartate aminotransferase (ALT) and alanine transaminase (ALT), creatine kinase (CK), urea nitrogen, were detected. Neurological function deficit was determined. The survival condition was surveyed 6 months after. RESULTS: (1) The TC and LDL-C decreased after treatment in the 3 groups with significant differences between Group A and Group C, Group B and Group C, and Group B and Group C (all P < 0.05). (2) The plasma level of hsCRP decreased by 9.1%, 33.9%, and 30.1% respectively 7 days after treatment in Groups A, B, and C with significant differences between Groups A and B and between Groups A and C (both P < 0.05), however, without significant difference between Group B and Group C. The level of hsCRP decreased by 34.3%, 56.0%, and 52.9% respectively 14 days after treatment in the 3 groups with significant differences between Groups A and B and between Groups A and C (both P < 0.05), however, without significant difference between Group B and Group C. (3) The level of IL-6 decreased 7 and 14 days after treatment in all 3 groups, however, without significant differences between any 2 groups (all P > 0.05). (4) The decrease of hsCRP and decrease of IL-6 were not correlated with the percentage of TC decrease (both P > 0.05) in Group B. The decrease of hsCRP was not correlated with the changes of blood lipids in Group C. (5) Both the plasma hsCRP and IL-6 before treatment were positively correlated with the infection volume and neurological function score (all P < 0.01). CONCLUSION: Atorvastatin has an anti-inflammatory action benefiting the alleviation of secondary inflammatory damaged in acute cerebral infarction that is independent of lipid lowering.

[Construction of the eukaryotic expression vector of MJD1 and its expression in SH-SY5Y cells].

OBJECTIVE: To construct the eukaryotic expression vector of MJD1 with normal copies of CAG trinucleotide repetition and MJD1 with CAG trinucleotide repetition expansion mutation respectively, and to determine whether the polyglutamine expansion in ataxin-3 could lead to the formation of intranuclear aggregation. METHODS: The coding sequence of wild-type MJD1 and mutant MJD1 was amplified by PCR from pAS2-1-MJD20Q and pAS2-1-MJD68Q respectively. After being digested with BamH I and Hind III, the PCR products were inserted into pcDNA3. 1-Myc-His(-) B. The recombinant plasmids pcDNA3.1-Myc-His(-) B-MJD20Q and pcDNA3.1-Myc-His(-) B-MJD68Q were identified by enzyme digestion analysis and DNA sequencing. The recombinant plasmid was transfected into SH-SYSY cells and the expression of MJD1 in the transfected cells was analyzed by Western blot. The immunofluorescence of the transfected cells was examined using a confocal microscope to observe the formation of intranuclear aggregation. RESULTS: Enzyme digestion analysis and DNA sequencing showed that the target gene was cloned into pcDNA3. 1-Myc-His(-) B. The expression of MJD1 in the transfected cells was confirmed by Western blot; The SH-SY5Y cells transfected with pcDNA3. 1-Myc-His(-) B-MJD68Q showed the formation of intranuclear aggregation, but the cells transfected with pcDNA3.1-Myc-His(-) B-MJD20Q did not show such phenomenon. CONCLUSION: The eukaryotic expression vectors of MJD1 has been successfully constructed; The polyglutamine expansion in ataxin-3 could lead to the formation of intranuclear aggregation.

Neuroprotective effects of atorvastatin against cerebral ischemia/reperfusion injury through the inhibition of endoplasmic reticulum stress.

Cerebral ischemia triggers secondary ischemia/reperfusion injury and endoplasmic reticulum stress initiates cell apoptosis. However, the regulatory mechanism of the signaling pathway remains unclear. We hypothesize that the regulatory mechanisms are mediated by the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α in the endoplasmic reticulum stress signaling pathway. To verify this hypothesis, we occluded the middle cerebral artery in rats to establish focal cerebral ischemia/reperfusion model. Results showed that the expression levels of protein kinase-like endoplasmic reticulum kinase and caspase-3, as well as the phosphorylation of eukaryotic initiation factor 2α, were increased after ischemia/reperfusion. Administration of atorvastatin decreased the expression of protein kinase-like endoplasmic reticulum kinase, caspase-3 and phosphorylated eukaryotic initiation factor 2α, reduced the infarct volume and improved ultrastructure in the rat brain. After salubrinal, the specific inhibitor of phosphorylated eukaryotic initiation factor 2α was given into the rats intragastrically, the expression levels of caspase-3 and phosphorylated eukaryotic initiation factor 2α in the were decreased, a reduction of the infarct volume and less ultrastructural damage were observed than the untreated, ischemic brain. However, salubrinal had no impact on the expression of protein kinase-like endoplasmic reticulum kinase. Experimental findings indicate that atorvastatin inhibits endoplasmic reticulum stress and exerts neuroprotective effects. The underlying mechanisms of attenuating ischemia/reperfusion injury are associated with the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/caspase-3 pathway.

The key target of neuroprotection after the onset of ischemic stroke: secretory pathway Ca(2+)-ATPase 1.

The regulatory mechanisms of cytoplasmic Ca(2+) after myocardial infarction-induced Ca(2+) overload involve secretory pathway Ca(2+)-ATPase 1 and the Golgi apparatus and are well understood. However, the effect of Golgi apparatus on Ca(2+) overload after cerebral ischemia and reperfusion remains unclear. Four-vessel occlusion rats were used as animal models of cerebral ischemia. The expression of secretory pathway Ca(2+)-ATPase 1 in the cortex and hippocampus was detected by immunoblotting, and Ca(2+) concentrations in the cytoplasm and Golgi vesicles were determined. Results showed an overload of cytoplasmic Ca(2+) during ischemia and reperfusion that reached a peak after reperfusion. Levels of Golgi Ca(2+) showed an opposite effect. The expression of Golgi-specific secretory pathway Ca(2+)-ATPase 1 in the cortex and hippocampus decreased before ischemia and reperfusion, and increased after reperfusion for 6 hours. This variation was similar to the alteration of calcium in separated Golgi vesicles. These results indicate that the Golgi apparatus participates in the formation and alleviation of calcium overload, and that secretory pathway Ca(2+)-ATPase 1 tightly responds to ischemia and reperfusion in nerve cells. Thus, we concluded that secretory pathway Ca(2+)-ATPase 1 plays an essential role in cytosolic calcium regulation and its expression can be used as a marker of Golgi stress, responding to cerebral ischemia and reperfusion. The secretory pathway Ca(2+)-ATPase 1 can be an important neuroprotective target of ischemic stroke.

Overexpression of chaperonin containing TCP1, subunit 3 predicts poor prognosis in hepatocellular carcinoma.

AIM: To investigate the value of chaperonin containing TCP1, subunit 3 (CCT3) to predict the prognosis of patients with hepatocellular carcinoma (HCC) and determine its function in HCC progression. METHODS: CCT3 expression levels were examined in human non-cancerous liver tissues and a variety of HCC cell lines by quantitative real-time PCR and immunoblotting. CCT3 expression was suppressed by small interfering RNA. The effects of reducing CCT3 expression in HCC cells were tested. The 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay, cell counting experiment, cell cycle assay, apoptosis assay and invasion assay were employed to evaluate cell functions in vitro. Immunohistochemistry was performed on HCC specimens. In addition, CCT3 expression in HCC specimens was also assessed at the protein and mRNA level. Associations between clinicopathological characteristics and prognosis were analyzed, along with the possible mechanisms involved in CCT3's function in HCC progression. RESULTS: The expression levels of CCT3 mRNA and protein were upregulated in HCC cell lines in contrast to adjacent non-cancerous tissues. Reducing CCT3 expression not only suppressed cell proliferation in cell counts, MTT assay, cell cycle assay and induced cell apoptosis (P < 0.05 vs negative control), but also inhibited the tumor cell invasion capacity in vitro (P < 0.01 vs negative control). Overexpression of CCT3 in the nuclei of cancer cells in HCC specimens (58 of 104 patients, 55.8%) was associated with poor prognosis in HCC patients (3-year survival rate, 55.5% vs 84.2%, P = 0.020) after hepatectomy. Mechanistic analyses showed that signal transducer and activator of transcription 3 (STAT3) activation was decreased even when stimulated by interleukin-6 after knocking down CCT3 in the HepG2 cell line. CONCLUSION: Overexpression of CCT3 in the nuclei of cancerous cells is associated with HCC progression. CCT3 may be a target that affects the activation of STAT3 in HCC.

De novo malignancy after liver transplantation: a single-center experience of 14 cases.

PURPOSE: The aim of this study is to evaluate the incidence of de novo malignancy after liver transplantation (LT) and compare with those among the general Chinese population. METHODS: A total of 466 patients who had a minimum follow-up time of 6 months were enrolled in the study. All data of medical records and follow up were retrospectively reviewed. RESULTS: The incidence rate of de novo malignancy was 3.0% (14 in 466 patients). The median elapsed time from transplant to the diagnosis of de novo malignancy was 42 months (range, 6 to 106 months). The cumulative risk for development of de novo malignancy was 1.6%, 2.7%, and 8.2% at 3, 5 and 10 years after LT, respectively. The patients were all male. The types of de novo tumors included digestive system tumor (8 in 14), lung cancer (2 in 14), urologic neoplasm (2 in 14), and hematologic malignant tumor (2 in 14). Over a mean follow-up of 24 months after diagnosis of de novo malignancy, 7 patients (50.0%) died; the overall 5-year patient survival rate was 54.5%. The relative risk of malignancy following LT was 9.5 folds higher than the general Chinese population. CONCLUSION: The relative risk of malignancy following LT was much higher than the general Chinese population. Digestive system tumor is the most common type of de novo malignancy after LT in China.