[Comparison of programmed death-ligand 1 protein expression between primary tumors and lymph node metastatic lesions in oral squamous cell carcinoma].

Objective: To investigate the difference of programmed death-ligand 1 (PD-L1) expression between primary lesions and lymph node metastatic lesions in oral squamous cell carcinoma. Methods: Eighty-two patients diagnosed with oral squamous cell carcinoma from December 2020 to July 2021 in Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine & College of Stomatology, Shanghai Jiao Tong University, were enrolled in this study. All the patients underwent neck dissection concurrently and had lymph node metastasis. Among them, there were 28 females and 54 males. The age range was 24-79 years old [(58.6±11.7) years old]. The expression of PD-L1 protein in primary tumors and lymph node metastatic lesions was detected by immunohistochemistry. Combined positive score (CPS) was used to evaluate the PD-L1 expression. And the difference of PD-L1 expression between primary tumors and metastatic lesions was analyzed. Results: Among 82 primary tumors, 9 cases (11%) had PD-L1 CPS<1, 31 cases (38%)≥ 1 and <20, and 42 cases (51%)≥20. Cases with perineural invasion had lower CPS (χ2=6.35, P=0.042). Among 82 matched lymph node metastatic lesions, 9 cases (11%) had CPS<1, 38 cases (46%)≥1 and<20, and 35 cases (43%)≥20. The CPS of 27 pairs (33%) of primary and metastatic lesions were discordant. The statistical results showed that the Kappa value of consistency evaluation was 0.446, indicating that the consistency of PD-L1 CPS in primary and metastatic lesions of OSCC was medium. Conclusions: There are differences in PD-L1 expression between the primary lesion of OSCC and cervical lymph node metastatic lesions, and the consistency is medium. In the routine practice, lymph node metastatic lesions should be carefully used to replace the primary lesion for PD-L1 CPS evaluating.

[Construction of a nomogram model for predicting 2-year survival rate of small cell lung cancer based on more comprehensive variables].

Objective: To construct a novel prognostic nomogram model based on more comprehensive variables for patients with small-cell lung cancer (SCLC). Methods: The data of 722 patients with SCLC confirmed by pathology in Affiliated Cancer Hospital of Shanxi Medical University from January 2015 to December 2018 were retrospectively analyzed [including 592 males and 130 females, aged from 23 to 82(61±9) years]. A random seed count of 133 was used to divide those patients into training set (n=422) and validation set (n=300). Kaplan-Meier was used for survival curves analysis and univariate Log-rank test was used for evaluating the influence of clinical variables on the prognosis of sclc, variables with P<0.05 in univariate analysis were included in a multivariate Cox regression model. The nomogram was constructed based on the variables which P<0.05 in multivariate analysis. Receiver operating characteristic (ROC) curve, calibration by Integrated Brier score (IBS) and clinical net benefit by decision curve analysis (DCA) were used to evaluate model discriminative power, prediction error value, and clinical net benefit, and compared with the American Joint Committee on Cancer 8th TNM. Results: Male, abnormal monocyte (MON) counts, abnormal neuron specific enolase (NSE), abnormal cytokeratin 19 fragment (Cyfra211), M1a stage, M1b stage, M1c stage, radiotherapy (RT), chemotherapy ≥4 cycles and prophylactic cranial irradiation (PCI) were prognostic factors for SCLC[HR(95%CI)=1.39(1.00-1.92), 1.29(1.02-1.63), 1.41(1.11-1.80), 2.02(1.48-2.76), 1.09(0.77-1.55), 1.44(0.94-2.22), 2.01(1.49-2.71), 0.75(0.57-0.98), 0.40(0.31-0.51)and 0.42(0.26-0.68), respectively, all P<0.05]. The area under ROC curve (AUC) of the nomogram in training set and validation set were 0.814(95%CI: 0.765-0.862)and 0.787 (95%CI: 0.725-0.849), which were higher than TNM [0.616(95%CI: 0.558-0.674) and 0.648(95%CI: 0.581-0.715)].The calibration curve showed a good correlation between the nomogram prediction and actual observation for the 2-year overall survival (OS). IBS indicted a lower prediction error rate (training set: 0.132 vs 0.169; validation set: 0.138 vs 0.169). DCA showed a wider threshold range than TNM (training set: 0.01-0.96 vs 0.01-0.85, validation set: 0.01-0.94 vs 0.01-0.86) and a greater improvement of the clinical net benefit (in training set the nomogram had a greater clinical benefit than TNM in the range of 0.19-0.96, and remained in validation set in the range of 0.19-0.94). Conclusion: The established nomogram model for predicting 2-year OS in patients with SCLC based on 8 variables, including gender, MON, NSE, Cyfra211, M stage, RT, CT cycles and PCI can be used for an more accurately prognosis prediction and reference for therapeutic regimen selection.

Large-scale preparation for efficient polymer-based room-temperature phosphorescence via click chemistry.

To achieve efficient polymer-based room-temperature phosphorescence (RTP) materials, covalently embedding phosphors into the polymer matrix appeared as the most appealing approach. However, it is still highly challenging to fabricate RTP materials on a large scale because of the inefficient binding engineering and time-consuming covalent reactions. Here, we have proposed a scalable preparation approach for RTP materials by the facile B─O click reaction between boronic acid-modified phosphors and polyhydroxy polymer matrix. The ab initio molecular dynamics simulations demonstrated that the phosphors were effectively immobilized, resulting in the suppressed nonradiative transitions and activated RTP emission. In comparison to the reported covalent binding time of several hours, such a B─O click reaction can be accomplished within 20 s under ambient environment. The developed strategy simplified the construction of polymer-based RTP polymeric materials by the introduction of facile click chemistry. Our success provides inspirations and possibilities for the scale-up production of RTP materials.

Central nervous disease in pediatric patients during acute lymphoblastic leukemia (ALL): a review.

Acute lymphoblastic leukemia (ALL) is one of the frequently reported malignancies of childhood age. Earlier it was thought to be a fatal pathological state with no cure, but with advancements in medicine and science, new therapeutic approaches have resulted in better management and cure. However, one of the major hurdles in achieving a complete cure is the relapse of ALL at extra-medullary sites like the central nervous system (CNS). The present review article is focused on recent diagnostic avenues available for the detection of CNS disease during acute lymphoblastic leukemia (ALL) in young patients.

Childhood multiple sclerosis: clinical features and recent developments on treatment choices and outcomes.

Multiple sclerosis (MS) is an inflammatory idiopathic autoimmune disease causing demyelination of central nervous system (CNS). The incidence of pediatric MS is relatively rare, affecting 0.2 to 0.64/100,000 subjects; cases with MS onset before age 10-12 years, account for less than 1% of all MS cases, while 2.7 to 10.5% of all MS cases worldwide are seen in children <18 years of age, with a strong female preponderance. The disease course of MS varies from a benign type with relatively low level of disability after a long duration (15 years) of the disease, to a malignant type of MS with severe disability or even death within few months following onset. Diagnostic criteria for pediatric MS include ≥ 2 clinical events involving more areas of CNS inflammation in the absence of encephalopathy, separated by > 30 days, along with the involvement of brainstem. Pediatric MS generally presents relapsing-remittent form of MS, with majority of the patients recovering from the first attack. Major histocompatibility complex, more specifically, mutations in the human leukocyte antigen (HLA) DRB1*15 allele, are considered most important genetic factors that are contributory to the disease. Treatment choices for pediatric MS include many disease-modifying therapies (DMT) that are currently being used for adult MS and these are interferon-ß 1a/1b (IFN-ß1a/1b), glatiramer acetate, teriflunomide, dimethyl fumarate, alemtuzumab, etc. However, most of these have not gone through complete testing in randomized, placebo-controlled clinical trials for pediatric MS and are being prescribed off-label by clinicians. As these studies are progressing, it is important to address if these approaches of treating pediatric MS patients have any long-term impact on patients, in particular, physical, cognitive, developmental and social outcomes of the children.

Lymphocyte subsets in children with hemophagocytic lymphohistiocytosis (HLH) and its clinical significance.

OBJECTIVE: To study the peripheral blood lymphocyte subsets in children with hemophagocytic lymphohistiocytosis (HLH) in acute period as well as remission period, and compare them with healthy children to investigate the significance of lymphocyte subsets in the diagnosis, treatment, and prognosis in children with HLH. PATIENTS AND METHODS: From January 2009 to March 2014, 30 HLH patients were enrolled in this study. Among them, 20 were placed in the remission group, while 10 cases were placed in the death group. 6 cases died within 8 weeks due to the illness, and 4 cases died within 9 to 34 weeks. 30 children who were confirmed healthy after physical check-ups in the same period were enrolled in the control group. Peripheral blood was collected from both groups and lymphocyte subsets were studied using flow cytometry. RESULTS: The ratios of CD3+ T and CD8+ T cells increased in the HLH remission group and the death group, while CD4+, CD4+/CD8+ and CD3-CD16+CD56+NK ratios decreased. Difference detected in the proportion of CD19+ B cells was not statistically significant. By comparing lymphocyte subsets in the HLH acute period and the remission period in HLH patients we discovered that the differences in CD3+, CD8+, CD4+ and CD4+/CD8+, CD19+ B cells ratios were not statistically significant (p > 0.05). CD3-CD16+CD56+NK cells ratios in the remission period increased significantly. CONCLUSIONS: The lymphocyte subsets in children with HLH underwent obvious changes and there was an imbalance in cellular immunity. We believe that dynamic detection of changes may help us to evaluate the prognosis and the effect of the treatment.

Recent perspectives of pediatric leukemia - an update.

Leukemia is defined as an aberrant hyper-proliferation of immature blood cells that do not form solid tumor masses (i.e., liquid cancer). Usually, leukemia could be either of the myeloid or lymphoid lineages, and is classified as acute or chronic in nature. Chronic leukemias tend to have more mature cells and are rare in pediatric patients. Acute leukemias, on the other hand, are typically less mature and commonly occur in patients of all ages and are potentially rapidly fatal if not readily treated. The acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Similar to AML, and in some cases, on the same disease spectrum, are the myelodysplastic syndromes (MDS). The present review is focused on the recent perspectives of pediatric leukemia.

Current views of common pediatric cancers - an update.

Advancements in pediatric cancers diagnostics clarity and treatments have greatly increased survival rates in the pediatric oncology population. Increased survival rates have turned new attention to studying psychosocial stressors and improvisation of the quality of life of the suffering cancer patients. The cancer treatment experience could be divided into three phases: diagnosis, treatment, and post-treatment/survivorship. The present review article would focus specifically on the three most common pediatric cancer diagnostic categories viz. acute lymphoblastic leukemia (ALL), central nervous system (CNS) tumors, and neuroblastoma.

Macrophage activation syndrome as a complication of juvenile rheumatoid arthritis.

OBJECTIVE: Juvenile rheumatoid arthritis (JRA), also known as juvenile idiopathic arthritis (JIA), is a rare autoimmune joint disorder of children. The concrete causes for the prevalence of the above pathological state are still unknown. In other words, it is an arthritis affecting mainly children and adolescents. Clinically, it has 3 different clinical subtypes. JRA patients are often noticed with some confirmed symptoms including coagulopathy, disseminated intravascular coagulation (DIC) with hepatosplenomegaly, fall in erythrocyte sedimentation rate and higher levels of liver enzymes leading to a life-threatening outcome. The above complications of JRA are recognized as a macrophage activation syndrome (MAS), which is similar to hemophagocytic lymphohistiocytosis (HLH). Pathogenesis of JRA manly involves deregulation of immunological processes with excessive and persistent activation of antigen presenting cells and T-lymphocytes. Further, abnormalities in the functioning of NK cells are often observed in JIA cases. Also, 40% of patients with these abnormalities are habitually associated with perforin gene mutations. Today, MAS remains a clinical and diagnostic challenge. RESULTS: The diagnosis of MAS is mainly based on clinical grounds. However, laboratory evidence of macrophages in the bone marrow performing phagocytosis of variable hematopoietic cells also help in diagnosis. For confirmation of MAS, there must be present either of two clinical or laboratory criteria. Further, laboratory criteria often appear late and are unable to diagnose the complication right at the beginning stage. Important laboratory findings in macrophage activation syndrome associated with JIA include hypertriglyceridemia, anemia, low erythrocyte sedimentation rate, elevated alanine aminotransferase level, higher than normal bilirubin levels, presence of fibrin degradation products, high lactate dehydrogenase level, low sodium, low albumin, and hyperferritinemia. CONCLUSIONS: MAS is a confirmed life threatening complication of patients with JIA. Further, an early diagnosis and treatment of MAS could be a life-saving mode for this syndrome.

[Preliminary experience with transoral endoscopic thyroidectomy via vestibular approach: a report of 150 cases in a single center].

Objective: To summarize the preliminary experience with transoral endoscopic thyroidectomy via vestibular approach (TOETVA). Methods: A total of 150 consecutive patients with thyroid disease underwent TOETVA from November 2014 to February 2017 at Department of Thyroid Surgery, the Second Affiliated Hospital of Zhejiang University School of Medicine. The patients were comprised of 138 females and 12 males. The mean age of the patients was (31.7±7.6) years (ranging from 15 to 51 years). There were 108 patients of differential thyroid carcinoma (T1 or T2 ≤3 cm, cN0 or cN1a, M0) and 42 patients of benign thyroid disease (solid nodule ≤6 cm). The criteria analyzed were clinicopathologic characteristics, types of operation, operation time, complications and results of follow-up. Results: Two cases were converted into open surgery due to an incredible unexpected tumor size and tracheal invasion, respectively. One hundred and three patients with papillary carcinoma underwent transoral central neck dissection (CND), with the mean operation time of (146±34) minutes for hemithyroidectomy with CND, and (187±36) minutes for total or near total thyroidectomy with CND. The mean number of lymph node yields was 8.2±4.7, and the lymph node metastasis rate was 41.7% (43/103). Regarding postoperative complications, transient hoarseness occurred in 3 patients, and permanent recurrent laryngeal nerve occurred in 2 patients. One patient had local infection or transient mental nerve palsy. Transient hypocalcemia occurred in 31.8% of 22 patients who underwent total, near-total, or subtotalthyroidectomy, and no permanent hypocalcemia was registered. Mean hospital stay after operation was (3.5±0.6) days (ranging from 2 to 5 days). Mean follow-up period was (11.5±7.8) months (ranging from 1 to 28 months), no recurrence or metastasis occurred. Conclusions: TOETVA is feasible and safe for strictly selective patients. It brings perfect cosmetic effect. Long-term follow-up and further study is needed to assess its curative effect.

The WNT/ß-catenin signaling pathway may be involved in granulosa cell apoptosis from patients with PCOS in North China.

INTRODUCTION: Investigate the expressions of WNTs in granulosa cells of PCOS in North China, and explore the possible mechanism. MATERIAL AND METHODS: Patients with PCOS (n=40) and controls without PCOS (n=20) were enrolled into the study. The levels of serum sex hormone were detected by chemiluminescent enzyme immunoassay. RT-qPCR was used to measure mRNA levels of WNT family members (WNT1, WNT3, WNT4, WNT5, sFRP4 and sFRP5). The levels of Bax and Bcl-2 were measured by enzyme-linked immunosorbent assay. RESULTS: The levels of PROG, TES and LH/FSH had difference (p<0.05) on third day of menstrual cycle between PCOS and control groups. After injection of HCG, the levels of LH, E2 and PROG had significant difference (p<0.05). The PCOS group had higher transcript levels of WNT1, WNT3 and WNT4 (p<0.05), compared to controls. The level of secreted frizzled-related protein (sFRP4) was lower level in PCOS patients (p<0.05). In addition, we found a significant reduction of the ß-catenin as well as the downstream targets (survivin and BMP4) (p<0.05). The level of Bax was significantly higher in PCOS group than in the control group (p<0.05). Above all, the WNT/ß-catenin signaling pathway might be involved into granulosa cell apoptosis, which may provide a strategy for clinical treatment.

A review of risk factors for childhood leukemia.

OBJECTIVE: Leukemia is the most common cancer of childhood, with AML, CML, ALL and CLL being the most common. Environmental and genetic factors have been studied extensively in children with childhood leukemia. Other factors, such as the prenatal parental use of controlled substances, have not been investigated to the same degree. We review what is currently known about environmental and parental factors and the occurrence of leukemia in children. MATERIALS AND METHODS: Electronic databases were searched for studies correlated pediatric leukemia with (1) ionizing radiation; (2) benzene; (3) parental drug use (4) parental alcohol use; (5) genetic factors. RESULTS: The two known significant environment risk factors for the occurrence leukemia are ionizing radiation and benzene. However, at least 4 studies have been published over the last century have looked at other environmental factors such as pesticides and drug and alcohol use as well as genetic factors such as gene fusions and translocations. CONCLUSIONS: We determined the risk of environmental and genetic factors that could be the cause of childhood leukemia in an effort to reduce the incidence of this disease.

FSHR gene Thr307Ala and Asn680Ser polymorphisms in infertile men: an association study in North China and meta-analysis.

Male infertility is a complex multifactorial and polygenic disease, and genetic factors play an important role in its formation and development. Recently, the association between follicle stimulating hormone receptor (FSHR) gene polymorphisms and male infertility risk has attracted widespread attention due to the unique biological functions of FSH. The aim of this study was to further explore the associations between the Thr307Ala and Asn680Ser polymorphisms of the FSHR gene and male infertility. A case-control study of 212 infertile and 164 fertile men from North China was performed. FSHR polymorphism genotypes were obtained through direct DNA sequencing. A meta-analysis was also performed. In the single-site association analysis, no significant associations were identified between FSHR Thr307Ala and Asn680Ser polymorphisms and male infertility (P > 0.05). However, we found that the combined genotypic frequency of Thr/Ala + Asn/Asn was higher in infertile patients than in controls (6.6 vs 1.8%; odds ratio (OR) = 3.795; 95% confidence interval (CI): 1.072-13.434, P = 0.027). In the meta-analysis, there was also no evidence of FSHR polymorphism (rs 6165 and rs 6168) association with male infertility (P > 0.05). However, we found that the combined genotypes Thr/Thr + Asn/Asn had an increased risk of male infertility (OR = 1.238; 95%CI: 1.001-1.537, P = 0.049). Our studies further confirmed reports that there were no significant associations between the FSHR Thr307Ala and Asn680Ser polymorphisms and male infertility risk. However, a combined FSHR genotype showed significant association with male infertility.

Kaempferol Promotes Transplant Tolerance by Sustaining CD4+FoxP3+ Regulatory T Cells in the Presence of Calcineurin Inhibitor.

Calcineurin inhibitor cyclosporine is widely used as an immunosuppressant in clinic. However, mounting evidence has shown that cyclosporine hinders tolerance induction by dampening Tregs. Therefore, it is of paramount importance to overcome this pitfall. Kaempferol was reported to inhibit DC function. Here, we found that kaempferol delayed islet allograft rejection. Combination of kaempferol and low-dose, but not high-dose, of cyclosporine induced allograft tolerance in majority of recipient mice. Although kaempferol plus either dose of cyclosporine largely abrogated proliferation of graft-infiltrating T cells and their CTL activity, both proliferation and CTL activity in mice treated with kaempferol plus low-dose, but not high-dose, cyclosporine reemerged rapidly upon treatment withdrawal. Kaempferol increased CD4+FoxP3+ Tregs both in transplanted mice and in vitro, likely by suppressing DC maturation and their IL-6 expression. Reduction in Tregs by low dose of cyclosporine was reversed by kaempferol. Kaempferol-induced Tregs exhibited both allospecific and non-allospecific suppression. Administering IL-6 abrogated allograft tolerance induced by kaempferol and cyclosporine via diminishing CD4+FoxP3+ Tregs. Thus, for the first time, we demonstrated that kaempferol promotes transplant tolerance in the presence of low dose of cyclosporine, which allows for sufficient Treg generation while minimizing side effects, resulting in much-needed synergy between kaempferol and cyclosporine.

Cardioprotective effects mitochondrial ATP-sensitive potassium channel in exercise conditioning.

We investigated the mitochondrial ATP-sensitive potassium channel [mito-K (ATP)] in exercise preconditioning of myocardial ischemia-reperfusion injury in rats. Eighty SD rats were randomly divided into high-, moderate-, low-intensity, and control groups. The exercise groups were divided into control and inhibited groups. The control group was divided into model and sham groups. Eight rats were randomly selected from each group for analysis. At 40 and 50 min after ischemia-reperfusion, respectively, J point and T-wave values and QT intervals were significantly higher in the control model group than in the control sham group; ECG parameters were significantly lower in the exercise group than in the control group; ECG parameters were lower in the 5-HD-inhibited group than in the corresponding exercise model group. The trends of serum enzymes (serum muscle kinase isoenzyme, lactate dehydrogenase, aspartate transaminase) were consistent with ECG parameter changes at 40 and 50 min after ischemia and reperfusion, respectively. Compared with the sham group, the control model group showed significantly decreased left ventricular systolic pressure (LVSP) and maximum rate of left ventricular pressure development (dP/dtmax) and significantly increased left ventricular end-diastolic pressure (LVEDP). LVSP and dP/dtmax were significantly higher and LVEDP was significantly lower in the control group than in the exercise model group. LVSP and dP/dtmax were significantly lower and LVEDP was significantly higher in the inhibited group than in the corresponding exercise group. Long-term exercise can produce a preconditioning effect that exerts an ischemia-reperfusion cardioprotective effect. Mito-K (ATP) mediates the cardioprotective effects of exercise preconditioning.

The effect of TRPM7 suppression on the proliferation, migration and osteogenic differentiation of human dental pulp stem cells.

AIM: To investigate the role of the Ca(2+) -Mg(2+) ion channel TRPM7 in the proliferation, migration and osteogenic differentiation of human dental pulp stem cells (hDPSCs). METHODOLOGY: Immunohistochemistry was used to localize expression of TRPM7 in human dental pulp tissues and in cultured hDPSCs. Isolated hDPSCs were infected with recombinant lentiviruses expressing short hairpin RNA (shRNA) specific for TRPM7, or control shRNA, in order to suppress TRPM7 mRNA expression and investigate its functional role. The proliferation of the shRNA-infected hDPSCs was evaluated using both an MTT assay to measure viable cell numbers and cell cycle analysis. Cell migration was assessed using a transwell assay. The dynamic mRNA expression of TRPM7 during osteogenic differentiation of hDPSCs and the effect of shRNA specific for TRPM7 on hDPSC osteogenic differentiation were evaluated by real-time PCR. RESULTS: TRPM7 expression was widespread in human dental pulp tissue and was detected mainly in the cytomembrane and cytoplasm of hDPSCs. Suppression of TRPM7 inhibited both the proliferation and the migratory capacity of hDPSCs. TRPM7 mRNA expression was elevated during osteogenic differentiation of hDPSCs. TRPM7-specific shRNA inhibited osteogenic differentiation of hDPSCs, with downregulated mRNA expression of the osteogenic markers alkaline phosphatase (ALP), dentine sialophosphoprotein (DSPP), bone sialoprotein (BSP), runt-related transcription factor (RUNX2) and osterix (OSX). CONCLUSIONS: TRPM7 was involved in the regulation of hDPSC proliferation, migration and osteogenic differentiation and may play a role in the dental pulp repair process.

Antibacterial nanocomposite with calcium phosphate and quaternary ammonium.

Secondary caries is a frequent reason for restoration failure, resulting from acidogenic bacteria and their biofilms. The objectives of this study were to: (1) develop a novel nanocomposite containing nanoparticles of amorphous calcium phosphate (NACP) and quaternary ammonium dimethacrylate (QADM); and (2) investigate its mechanical and antibacterial durability. A spray-drying technique yielded NACP with particle size of 116 nm. The nanocomposite contained NACP and reinforcement glass fillers, with QADM in the resin. Two commercial composites were tested as controls. Composites were inoculated with Streptococcus mutans. After 180-day water-aging, NACP+QADM nanocomposite had flexural strength and elastic modulus matching those of commercial controls (p > 0.1). NACP+QADM nanocomposite reduced the biofilm colony-forming units (CFU) by 3-fold, compared with commercial composites (p < 0.05). Metabolic activity and lactic acid production of biofilms on NACP+QADM were much less than those on commercial composites (p < 0.05). The antibacterial properties of NACP+QADM were maintained after water-aging for 30, 90, and 180 d (p > 0.05). In conclusion, the novel NACP-QADM nanocomposite greatly decreased biofilm metabolic activity, CFU, and lactic acid, while matching the load-bearing capability of commercial composites without antibacterial properties. The NACP-QADM nanocomposite with strong and durable antibacterial properties, together with its previously reported Ca-PO(4) release capability, may render it useful for caries-inhibiting restorations.

[Inositol 1,4,5-triphosphate receptors (IP(3)Rs) in myocardial nuclei involved in pressure overload-induced hypertrophy of rat heart].

In order to clarify the importance of nuclear IP(3)Rs in the development of myocardial hypertrophy, a hypertensive rat model was established by abdominal aortic constriction, and velocity and isopyknic gradient centrifugation was employed to fractionate the cardiac nuclei. The maximal number of binding sites (B(max)) and dissociation constant (Kd) of IP(3) to the nuclear envelopes were measured by [(3)H] IP(3) binding assay. The existence of IP(3)Rs on myocardial nuclear envelope was confirmed. [Ca(2+)] inhibited [(3)H] IP(3) binding to its receptors in cardiac nuclear envelopes in a concentration-dependent way. Phosphorylation by CaM and endogenous PKC decreased B(max) of nuclear IP(3) receptors. B(max) and Kd of nuclear IP(3)Rs were increased by 1.217 (P<0.01) and by 2.149-fold (P<0.01) respectively in hypertrophic myocardium as compared with those of the control. The above results suggest that IP(3)Rs exist in myocardial nuclei and are down regulated by CaM, PMA and free Ca(2+). The increase of the binding sites of IP(3)Rs in the nuclear envelopes and the decrease of their affinity might play importment roles in the development of overload induction of cardiac hypertrophy.

[Effect of uncaria on evoked field potential of hippocampal slice in epileptogenic rat].

AIM: To investigate the effect of uncaria on evoked field potential of CA1 hippocampal slice in epileptogenic model. METHODS: We made rats which were injected by pilocarpine as epileptic-models. The pathway of drug administration is titration adjacent to hippocampal slices. We recorded the evoked field potential of hippocampal slice by glass microelectrode extracellularly, and observed the effect of uncaria on the amplitude of population spike (PS) in CA1 pyramidal cells in hippocampal slices. RESULTS: The uncaria with concentration of 1 g/ml could reduce the amplitude of PS in CA1 of hippocampal slices. The average of fall was 27.64%, and restored in 8.71 minutes on average (n = 14, P < 0.01). CONCLUSION: Uncaria could reduce the amplitude of PS in CA1 of epileptic hippocampal slices remarkably. These results show that uncaria can inhabited the synaptic transfer activity of CNS remarkably, suggest that it has the distinct effect of anti-epilepsy.