The brain-gut peptide ghrelin, a endogenous ligand for the growth hormone secretagogue hormone receptor, is mainly produced by gastric cells in the periphery, regulating energy metabolism via stimulating the appetite. Inside the brain, ghrelin is mainly expressed in the pituitary and in the hypothalamic arcuate nucleus, regulating the synthesis and secretion of neuropeptides that are correlated with feeding behavior, reproduction, and stress responses. Recently, more and more researches focused on the regulating roles of ghrelin on learning and memory, and mood regulation have indicated that ghrelin may inhibit neuronal apoptosis, improve cognitive function, and regulate the activities of neuroendocrine systems such as the hypothalamo-pituitary-adrenal axis and the hypothalamo-pituitary-gonadal axis thus get involved in the pathogenesis of neuropsychiatric diseases. The aim of this review is to summarize the main findings in this field, with the purpose of promoting further studies on the role of ghrelin in the brain.
Apoptosis ; Brain ; metabolism ; pathology ; physiology ; Ghrelin ; metabolism ; physiology ; Humans ; Learning ; Memory ; Neurons ; pathology ; Parkinson Disease ; metabolism ; pathology ; physiopathology

OBJECTIVETo study the relationship between estrogen receptor beta gene (ER beta) polymorphism and unknown aetiology hypomenorrhea in Southwestern China .

METHODSOne hundred eumenorrhea women were chosen as control group and another 100 hypomenorrhea patients as case group from Southwestern China. Restriction fragment length polymorphism (RFLP) of the Rsa I and Alu I in ER beta gene was analysed. The ER beta gene polymorphism genotype distribution in case group and control group was compared.

RESULTSR allele frequency in case and control groups was 37.5% and 48.5% respectively, the OR was 0.64 (95%CI: 0.42-0.97), P= 0.026. A allele frequency in case and control groups was 18.0% and 11.5% respectively, the OR was 1.69 (95%CI: 0.93-3.09), P= 0.07. RFLP of Rsa I and Alu I in both groups were distributed with polymorphism.

CONCLUSIONERbeta gene polymorphism has a relation with unknown aetiological hypomenorrhea. R allele may be the guard factor, and A allele may be its risk factor.

Adult ; Binding Sites ; genetics ; Deoxyribonucleases, Type II Site-Specific ; metabolism ; Estrogen Receptor beta ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Menstruation Disturbances ; etiology ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; Young Adult

Objective To investigate the effect of change in neurotrophins level in the bronchial asthma rats' lung on airway hyperresponsiveness and airway neural plasticity. Methods A total of forty male SD rats were randomly divided into 4 groups with 10 rats in each group: control group,asthmatic group, NGF+BDNF prevention group and anti-NGF+anti-BDNF prevention group. The asthmatic model was established by inhalation and injection of ovalbumin. The airway responsiveness was measured after 8 weeks.The bronchial inflammation was assessed by HE staining,and nerve growth factor and brain derived neurotrophic factor expressions of left lung were assayed by the immunohistochemistry staining.Then the expressions of synaptophysin and neurofilament were detected by RT-PCR. Results Compared with the control group, the lung tissue of the asthma group and NGF+BDNF prevention group had more infiltrating inflammatory cells; The expressions of NGF and BDNF were higher in the asthma group and NGF+BDNF prevention group than those in the control group and anti-NGF+anti-BDNF prevention group (P＜0.05),and significantly higher in the NGF+BDNF prevention group than those in the asthma group (P＜0.05).Both the airway responsiveness and the levels of SYN mRNA and NF mRNA in the lung tissues were significantly higher in the asthma group and NGF+BDNF prevention group than those in the control group (P＜0.05).In asthma group,the expressions of NGF and BDNF were positively related to the expressions of SYN (r=0.889,P＜0.05; r=0.985,P＜0.05)and NF(r=0.956,P＜0.05; r=0.927,P＜0.05),and also positively related to the airway hyperresponsiveness (r=0.938,P＜0.05; r=0.906,P＜0.05). Conclusion NGF and BDNF might be involved in rat airway bronchial neural plasticity changes,which resulted in the airway hyperresponsiveness.

OBJECTIVETo discuss the clinicopathological features and prognostic factors of gastric lymphoma.

METHODS83 gastric lymphoma cases were analyzed retrospectively in accordance to the criteria of the new World Health Organization classification for neoplastic diseases of the hematopoietic and lymphoid tissues. The correlations between clinicopathological features, therapeutic measures and survival were discussed.

RESULTSThe age of patients ranged from 25 to 77, with a median of 52. The number of males were similar to that of females. There were no specific symptoms. The most common symptoms were stomach ache (60 cases, 72%) or discomfort. The duration of symptoms was often long and with a history of chronic gastric diseases (21 cases, 25%). 13 cases had multiple lesions in the gastrointestinal mucosa. 51 cases (61%) were accompanied by lymph node involvement. According to the new World Health Organization classification for neoplastic diseases of the hematopoietic and lymphoid tissues, 57 cases were extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT)-type (MALT lymphoma), 23 were diffuse large B cell lymphoma accompanying MALT lymphoma, 2 were diffuse large B cell lymphoma and 1 was follicular lymphoma. Of all the cases, 31 were stage I E, 38 stage II E, 8 stage III E and 6 stage IV by the Ann Arbor staging system (1972). The total 5-year and 10-year survival rates were 77.8% and 70.1% respectively, with the mean survival time of 146 months. The 5-year and 10-year survival rates of MALT lymphoma were 77.4% and 72.3%, the 5-year and 10-year survival rates of diffuse large B cell lymphoma accompanying MALT lymphoma were 81.8% and 68.2%, the 5-year survival rate of diffuse large B cell lymphoma was 50.0%.

CONCLUSIONSThere are no specific symptoms in gastric lymphoma patients. Extranodal marginal zone lymphoma of MALT-type is the main histopathological type of gastric lymphoma, often accompanied by multiple mucosa involvement and also often accompanied by a history of chronic gastric disease. The lesion is usually localized for a long time, with a very good prognosis. Survival rate has a significant correlation with lymph node involvement and clinical stage. No correlations were found between the survival rates with age, gender, B symptoms, invasive depth of the wall of stomach, the size and range of the tumors or different therapeutic measures.

Adult ; Aged ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Gastrectomy ; methods ; Humans ; Lymphatic Metastasis ; Lymphoma ; pathology ; surgery ; therapy ; Lymphoma, B-Cell ; pathology ; surgery ; therapy ; Lymphoma, B-Cell, Marginal Zone ; pathology ; surgery ; therapy ; Lymphoma, Large B-Cell, Diffuse ; pathology ; surgery ; therapy ; Male ; Middle Aged ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Retrospective Studies ; Stomach Neoplasms ; pathology ; surgery ; therapy ; Survival Rate

OBJECTIVETo evaluate the efficacy and safety of Capsule metadoxine in the treatment of alcoholic liver disease.

METHODSA randomized double blind multicenter placebo-controlled clinical study was performed to evaluate the therapeutic effectiveness and safety of capsule metadoxine. Patients in metadoxine group received capsule metadoxine 500mg tid po. Patients in placebo group received placebo 2 pillows tid po. The treatment duration was 6 weeks. Patients were followed up 2 weeks after the treatment. Patients were visited once every 3 weeks during the treatment period. Clinical symptoms and liver function were evaluated in all the patients before treatment, at week 3, week 6 and 2 weeks after therapy. CT scan was done in some patients before treatment and at the end point of therapy.

RESULTS254 patients were recruited in the study, 126 in metadoxine group and 128 in placebo group. Median ALT, AST, GGT level in metadoxine group were decreased from 80.0 U/L, 59.2 U/L, 123.0 U/L (before treatment) to 41.1 U/L, 36.0 U/L, 57.0 U/L (after 6 weeks therapy). The improvement in liver function was more significant in metadoxine group than in placebo group (P less than 0.05). For the patients who stopped drinking during the study, the total effective rate of improvement in liver function was 82.8% in metadoxine group, much higher than that in placebo group (55.7% , P=0.0000). For the patients who did not stop drinking during the study, the total effective rate of improvement in liver function was 65.4% in metadoxine group, which is not significantly higher than that in placebo group (44.8%, P=0.1767). The CT value ratio of liver to spleen was significantly improved in metadoxine group (P=0.0023), and there was no significant difference between the two groups (P=0.6293). The rate of adverse was 1.6% in both of groups.

CONCLUSIONCapsule metadoxine is an effective and safe treatment for alcoholic liver disease.

Administration, Oral ; Adult ; Aged ; Alanine Transaminase ; blood ; Alcohol Deterrents ; administration & dosage ; therapeutic use ; Analysis of Variance ; Aspartate Aminotransferases ; blood ; Capsules ; Double-Blind Method ; Drug Combinations ; Fatty Liver, Alcoholic ; blood ; drug therapy ; pathology ; Female ; Follow-Up Studies ; Humans ; Liver ; diagnostic imaging ; pathology ; Liver Diseases, Alcoholic ; blood ; drug therapy ; pathology ; Liver Function Tests ; Male ; Middle Aged ; Pyridoxine ; administration & dosage ; therapeutic use ; Pyrrolidonecarboxylic Acid ; administration & dosage ; therapeutic use ; Treatment Outcome ; Ultrasonography ; Young Adult ; gamma-Glutamyltransferase ; blood

OBJECTIVEIt is important to use noninvasive methods to differentiate liver fibrosis and liver cirrhosis. A prospective study was conducted to evaluate the validity of ultrasonography (US) in evaluating the severity of liver fibrosis in patients with chronic viral hepatitis in reference to the pathologic diagnosis of their liver biopsy specimens.

METHODSThe liver fibrosis status of 324 chronic viral hepatitis patients was evaluated by both needle biopsy and US. Histologically their liver fibrosis was graded as S0-S4, and the inflammatory reaction in the liver was graded as G1-G4. The US examination included qualitative description of the liver surface and liver parenchyma, and the quantitative parameters were vascular diameters, blood flow volume and spleen size.

RESULTSUS qualitative description of the liver surface and liver parenchyma was correlated to the severity of fibrosis and the degree of the inflammation seen in the liver biopsies. An analysis of US quantitative parameters showed that a cut-off value of 12.1 cm for the length of spleen had a sensitivity of 60.0%, and specificity of 75.3% in detecting early liver fibrosis. For other quantitative parameters, the cut-off values were 8mm for the diameter of the splenic vein, 30.5 cm/sec for maximal blood flow velocity in the portal vein and 12 mm in diameter of the main portal vein. The diagnostic sensitivities for these parameters were 60.0%, 78.6% and 76.7%; the diagnostic specificities were 78.1%, 66.9% and 44.6% respectively.

CONCLUSIONEarly cirrhosis can be detected by US, and the sonographic results were well paralleled with their pathologic diagnoses made by liver biopsies. Individual US parameter has limited sensitivity and specificity in diagnosing early cirrhosis. In clinical practice a combination of 2-3 parameters could be used to detect or exclude severe liver fibrosis.

Adult ; Female ; Hepatitis B, Chronic ; complications ; diagnostic imaging ; Hepatitis C, Chronic ; complications ; diagnostic imaging ; Humans ; Liver Cirrhosis ; diagnostic imaging ; virology ; Male ; Prospective Studies ; Ultrasonography

Cell Differentiation ; Cell Line, Tumor ; metabolism ; Cell Proliferation ; Humans ; Trans-Activators ; biosynthesis ; genetics ; Transfection

Objective To investigate the validity of screw-rod system for fixing pelvic fractures by comparing the biomechanical behaviors from using screw-rod system or steel plate for fixing Tile B2 type pelvic fractures. Methods The finite element models of normal pelvis including ligaments, and Tile B2 fractured pelvis fixed by different screw-rod fixations (2 screws at fractured side, 3 screws at fractured side and at healthy side), and steel plate fixation were established. The vertical load (500 N) was applied on the upper terminal plate of the first body of the sacrum to simulate pelvis load during double-leg standing, single-leg standing and sitting. The displacement and stress distributions on normal pelvis and fractured pelvis with screw-rod fixation or with steel plate fixation were compared and analyzed. Results Both the screw-rod system and steel plate could effectively fix the fractured pelvis, and the fixation models showed similar displacement and stress distribution as normal pelvis. The largest displacement of fractured pelvis with 3-screw fixation on the diseased side was smallest under each working condition, and its stress level was also obviously lower than that of the other internal fixation models. During double-leg standing, compared with 2 screws fixation, 3 screws at healthy side fixation, and steel plate fixation, the Von Mises stress for 3 screws at fractured side fixation was reduced by 30.4%, 20.8%, 20.3%; during single-leg standing, the Von Mises stress for 3 screws at fractured side fixation was reduced by 31.8%,25.4%,18.5%; during sitting, the Von Mises stress for 3 screws at fractured side fixation is reduced by -6.5%,28.0%,61.1%,respectively. Conclusions The screw-rod system can fix Tile B2 pelvic fracture effectively, especially for 3-screw fixation on the fractured side. The results can provide the theory basis for clinical treatment of pelvic fracture.

OBJECTIVETo evaluate the efficacy and safety of Magnesium isoglycyrrhizinate in treatment of chronic liver diseases.

METHODSIt is a randomized, double-blind, multi-doses, active drug controlled, multi-center study. 480 proper patients were randomly divided into group A (180 patients), group B (180 patients) or group C (120 patients). Patients in group A received magnesium isoglycyrrhizinate 100 mg once daily. Patients in group B received magnesium isoglycyrrhizinate 150 mg once daily. Patients in group C received compound glycyrrhizin 120 mg once daily. The treatment course was 4 weeks. Patients were followed up 2 weeks after the treatment. Patients visited once every 2 weeks. Clinical symptoms, ALT, AST were evaluated in all the patients before treatment, at week 2, at week 4 and at 2 weeks later after treatment. The other liver function test was done before treatment and at week 4.

RESULTS412 patients completed the study according to the protocol,152 in group A, 160 in group B and 100 in group C. ALT and AST level were significantly decreased in all groups at week 2 and week 4 (P < 0.05). The degree of ALT decrease is greater in group B than in group C at week 2 (P < 0.01). The degree of ALT decrease was not significant different among three groups at week 4 (P > 0.05). The rates of ALT improvement at week 4 in group A, B, C were 92.59%, 91.76%, 88.29%, respectively (P > 0.05). The rates of symptoms improvement at week 4 in group A, B, C were 90.41%, 89.86%, 86.46% and 72.22%, 73.53%, 68.47%, respectively (P > 0.05). No relapse were found in all three groups after treatment. The rate of adverse event in three groups was similar (P > 0.05).

CONCLUSIONMagnesium isoglycyrrhizinate is an effective and safe treatment for chronic liver diseases.

Alanine Transaminase ; blood ; Anti-Inflammatory Agents ; adverse effects ; pharmacology ; therapeutic use ; Aspartate Aminotransferases ; blood ; Chronic Disease ; Double-Blind Method ; Fatty Liver ; blood ; drug therapy ; Female ; Glycyrrhizic Acid ; adverse effects ; pharmacology ; therapeutic use ; Humans ; Injections, Intravenous ; Liver ; drug effects ; pathology ; Liver Diseases ; blood ; drug therapy ; Liver Diseases, Alcoholic ; blood ; drug therapy ; Male ; Saponins ; adverse effects ; pharmacology ; therapeutic use ; Triterpenes ; adverse effects ; pharmacology ; therapeutic use

Objective: To clarify the molecular basis of patients with Bartter syndrome type I and explore the therapeutic effect of trafficking-defective variations by chemical chaperone 4-Phenylbutyric acid(4-PBA). Methods: The clinical characteristics, laboratory findings and genetic data of 3 patients diagnosed with Bartter syndrome type I who were admitted to Department of Nephrology, Children's Hospital of Nanjing Medical University from 2017 to 2018 were retrospectively analyzed. Wild type and variant SLC12A1 gene constructs were transiently overexpressed in HEK293 cells. Western blotting was used to detect the expression levels of Na⁺-K⁺-2Cl^-cotransporter(NKCC2) protein. Immunofluorescent staining was applied to investigate the subcellular localization of NKCC2 protein. In addition, the effect of the chemical chaperone 4-PBA on the expression and localization of the SLC12A1 gene variants was investigated. Unpaired t test was used for statistical analysis of 4-PBA treatment. Results: All the 3 patients (2 males and 1 female), aged 3.0, 4.0 and 1.2 years, respectively. All patients had antenatal onset with polyhydramnios and were born prematurely. After birth, all patients presented with hypochlorine alkalosis accompanied by hypokalemia and hyponatremia. Sequencing analysis revealed that the 3 patients were homozygotes or compound heterozygotes for variants in the SLC12A1 gene. In HEK293 cells, the surface expression of NKCC2 in 3 variants (p.L463S, p.L479V, p.507-510del) are all lower than in wild type (0.718±0.039, 0.287±0.081, 0.025±0.156 vs. 1.001±0.028, t=5.92, 8.35, 30.49, all P<0.01). Moreover, the total protein expression of p.L479V and p.507-510del group were all lower than that in wild type group (0.630±0.032, 0.043±0.003 vs. 1.000±0.111, t=3.21, 8.65, all P<0.05). 4-PBA treatment increased the mature protein expression level of the p.L463S and p. L479V group in 4-PBA treatment group are all higher than the untreated group (0.459±0.018 vs. 1.123±0.024, 0.053±0.012 vs. 1.256±0.037, t=2.75, 18.35, all P<0.05). Cytoplasmic retention of the L479V and 507-510del variants were observed by immunofluorescent staining. 4-PBA treatment could rescue a number of NKCC2 L479V variants to the membrane. Conclusions: The 3 SLC12A1 variants cause expression or subcellular localization defects of the protein. The findings that plasma membrane expression and activity can be rescued by 4PBA might help to develop novel therapeutic strategy for Bartter syndrome type Ⅰ.
Bartter Syndrome/genetics* ; Child, Preschool ; Female ; HEK293 Cells ; Homozygote ; Humans ; Infant ; Male ; Pregnancy ; Retrospective Studies ; Solute Carrier Family 12, Member 1/genetics*