Betulinic Acid Improves Cardiac Function in Septic Rats Through AKT / mTOR and AKT / AMPK -modulated Autophagy / 中国生物化学与分子生物学报

Betulinic acid (BA) exerts protective effects on organs in septic animals. However, whether BA can improve cardiac function in sepsis and the underlying mechanism remain unclear. Here, male Sprague-Dawley rats were pretreated with BA (25 mg/ kg/ d, i. g.) for 5 days and then intraperitoneally injected with lipopolysaccharide (LPS, 10 mg/ kg). The rats were anesthetized to determine transthoracic echocardiography using a high-resolution imaging system for small animals after they were treated with LPS for 6 h. Histopathologic alterations were examined by HE staining. Myocardial injury markers (cTnI and CK-MB) and inflammatory factors (TNF-α, IL-1β and IL-6) in the serum were measured by the enzyme-linked immunosorbent assay. Autophagy-related proteins (p62 and LC3 Ⅱ) and AKT-modulated autophagy pathways in the myocardium were determined by Western blotting. Pretreatment with BA markedly improved left ventricular ejection fraction (EF) and fraction shortening (FS) (P<0. 05), improved myocardial histomorphology, and significantly inhibited cTnI, CK-MB, TNF-α, IL-1β and IL-6 (P<0. 05) in the septic rat serum. BA markedly decreased p62 (P<0. 01), increased LC3 Ⅱ (P< 0. 001), and significantly down-regulated p-AKT (Thr308), p-AMPKα (Ser485/ 491), p-mTOR (Ser2448) and p-S6K (Thr389) (P<0. 05), while markedly up-regulated p-AMPKα (Thr172) and pULK1 (Ser317) (P<0. 01) in septic rat hearts. The findings indicate that BA can attenuate sepsis-induced myocardial dysfunctions associated with down-regulating autophagy inhibiting pathways mediated by AKT/ mTOR and AKT/ AMPK pathways.

Core prescriptions in treatment of edema by traditional Chinese medicine masters and mechanism prediction / 中国中药杂志

The core prescriptions and formulation characteristics in the treatment of edema by traditional Chinese medicine(TCM) masters were analyzed through data mining and their mechanisms were explored by network pharmacology. We collected journal reports on the treatment of edema by TCM masters in three sessions from China National Knowledge Infrastructure(CNKI) and constructed a database by Traditional Chinese Medicine Inheritance Support System 3.0. The prescriptions in the case studies were analyzed by association rules and k-means clustering. The chemical components and targets of Chinese medicines in core prescriptions were collected through TCMSP and TCMID. Edema-related targets were collected from DrugBank and GeneCards. The protein-protein interaction(PPI) network was constructed by STRING and the core targets were screened out. FunRich 3.1.3 was used to enrich the expression sites of core prescriptions. Metascape was used to perform Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis of intersection targets. Cytoscape 3.6.0 was used to visualize the "Chinese medicine-active ingredient-core target-pathway" network. The results showed that 315 pieces of medical records in the treatment of edema by TCM masters were obtained and five core prescriptions were analyzed by association rules and k-means clustering. Core prescription 1 contained Poria, Atractylodis Macrocephalae Rhizoma, Astragali Radix, Alismatis Rhizoma, Glycyrrhizae Radix et Rhizoma, and Codonopsis Radix, involving 166 chemical components and 1 125 targets. Core prescription 2 contained Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Poria, Chuanxiong Rhizoma, Paeoniae Radix Rubra, and Angelicae Sinensis Radix, involving 138 chemical components and 1 112 targets. Core prescription 3 contained Poria, Salviae Miltiorrhizae Radix et Rhizoma, Astragali Radix, Atractylodis Macrocephalae Rhizoma, Alismatis Rhizoma, and Coicis Semen, involving 126 chemical components and 1 121 targets. Core prescription 4 contained Poria, Forsythiae Fructus, Atractylodis Macrocephalae Rhizoma, Imperatae Rhizoma, Cicadae Periostracum, and Coicis Semen, involving 58 chemical components and 820 targets. Core prescription 5 contained Poria, Atractylodis Macrocephalae Rhizoma, Astragali Radix, Alismatis Rhizoma, Trionycis Carapax, and Dioscoreae Rhizoma, involving 68 chemical components and 919 targets. The core targets of core prescriptions included AKT1, ALB, CASP3, MAPK3, EGFR, SRC, MAPK1, and TNF. The potential targets of core prescriptions in the treatment were highly expressed in the stomach, bladder, lung, and kidney. KEGG pathways were enriched in inflammation and cell cycle pathways, especially the inflammation-relation pathways. The therapeutic effect of core prescriptions on edema is presumedly achieved by tonifying the spleen, draining water, activating blood, and benefiting Qi to resist inflammation and regulate the immune system. This study is expected to provide references for the summary of TCM masters' experience and new drug development.

Bushen Huoxue Recipe Inhibited Vascular Calcification in Chronic Renal Failure Rats by Regulating BMP-2/Runx2/Osterix Signal Pathway / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Bushen Huoxue Recipe (BHR) on inhibiting vascular calcification (VC) in chronic renal failure (CRF) rats by regulating BMP-2/Runx2/Osterix signal pathway, and to explore its possible mechanism.</p><p><b>METHODS</b>Thirty SD rats were randomly divided into the normal group, the model group, and the BHR group, 10 in each group. Rats in the model group and the BHR group were administered with 250 mg/kg adenine suspension by gastroagavage and fed with 1.8% high phosphorus forage, once per day in the first 4 weeks, and then gastric administration of adenine suspension was changed to once per two days in the following 5-8 weeks. Rats in the BHR group were administered with BHR at the daily dose of 55 g/kg by gastrogavage in the first 8 weeks, once per day. Equal volume of normal saline was given to rats in the normal group by gastrogavage for 8 weeks. Histological changes in renal tissue and aorta VC were observed by HE staining and alizarin red staining respectively. Levels of calcium (Ca), phosphorus (P), serum creatinine (Cr), blood urea nitrogen (BUN), and intact parathyroid hormone (iPTH) in serum were detected. Protein expression levels of bone morphogenetic protein (BMP-2), Runt related transcription factor (Runx2) , and Osterix were detected by Western blot.</p><p><b>RESULTS</b>HE staining showed that compared with the normal group, disordered glomerular structure, tubular ectasia and dropsy, intracavitary inflammatory cell infiltration, dark brown crystal deposition in kidney tubules, renal interstitial fibrosis, and decreased number of renal blood vessels in the model group. Compared with the model group, normal glomerular numbers increased more, reduced degree of tubular ectasia, decreased number of inflammatory cells, and reduced adenine crystal deposition in the BHR group. Alizarin red staining showed that compared with the normal group, calcified nodes could be found in the model group, with extensive deposition of red particle in aorta. Compared with the model group, calcified nodes were reduced in the BHR group. Compared with normal group, serum levels of P, SCr, BUN, and iPTH significantly increased, serum Ca level significantly decreased, protein expressions of BMP-2, Runx2, Osterix also increased in the model group (P < 0.05, P < 0.01). Compared with the model group, serum levels of P, SCr, BUN, and iPTH levels significantly decreased, serum Ca level significantly increased, protein expressions of BMP-2, Runx2, Osterix also decreased in the BHD group (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>BHD could improve renal function, Ca-P metabolism, and renal histological changes in CHF rats, down-regulate the expression level of BMP-2/Runx2/Osterix signal pathway in vascular calcification of CRF, which might be one of the mechanisms for inhibiting VC in CHF.</p>

Comparison of the Predictive Values of Eight Staging Systems for Primary Liver Cancer in Prognosis of Combined Hepatocellular-cholangiocellular Carcinoma Patients after Surgery / 中国医学科学院学报

<p><b>OBJECTIVE</b>To compare the predictive values of eight staging systems for primary liver cancer in the prognosis of combined hepatocellular-cholangiocellular carcinoma (cHCC-CC) patients after surgery.</p><p><b>METHODS</b>The clinical data of 54 cHCC-CC patients who underwent hepatectomy or liver transplantation from May 2005 to Augest 2013 in Chinese PLA General Hospital were collected. We evaluated the prognostic value of the Okuda staging system, Cancer of the Liver Italian Program (CLIP) score, French staging system, Barcelona Clinic Liver Cancer (BCLC) staging system, 7th edition of tumour-node-metastasis (TNM) staging system for hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC), Japan Integrated Staging (JIS) score, and Chinese University Prognostic Index. The distribution, Kaplan-Meier method, Log-rank test, and area under a receiver operating characteristic curve were used to compare the prognosis-predicting ability of these different staging systems in 54 cHCC-CC patients after surgery.</p><p><b>RESULTS</b>The TNM staging system for ICC and JIS score had a better distribution of cases. The 12-and 24-month survivals of the entire cohort were 65.5% and 56.3%, respectively. A Log-rank test showed that there was a significant difference existing in the cumulative survival rates of different stage patients when using TNM staging system for ICC (stage 1 vs. stage 2, P=0.012; stage 2 vs. stage 3-4, P=0.002), Okuda staging system (stage 1 vs. stage 2, P=0.025), and French staging system (stage A and stage B, P=0.045). The 12-and 24-month area under curve of TNM staging system for ICC, BCLC staging system, JIS score, and CLIP score were 0.836 and 0.847, 0.744 and 0.780, 0.723 and 0.764, and 0.710 and 0.786, respectively.</p><p><b>CONCLUSION</b>The 7th edition of TNM staging system for ICC has superior prognostic value to other seven staging systems in cHCC-CC patients undergoing surgical treatment.</p>

Intrahepatic biliary cystadenoma: experience with 10 consecutive cases at a single center / 南方医科大学学报

<p><b>OBJECTIVE</b>To summarize the clinical experience with diagnosis and treatment of intrahepatic biliary cystadenoma (IBCA).</p><p><b>METHODS</b>We retrospectively analyzed the data of 10 consecutive IBCA cases treated in our department in light of the characteristics of the epidemiology, radiology, lab tests, pathology and prognostic.</p><p><b>RESULTS</b>The patients are all female with an average age of 48.9 (16-73) years. The number of asymptomatic, slightly symptomatic and severe symptomatic patients was 4, 4 and 2, respectively. Radiological examination showed segmented cystic lesions in all the cases with an average diameter is 13.3∓4.9 cm. The incidence of segmentation, papillary or nodular hyperplasia, and calcification within the lesions was 90%, 60% and 20%, respectively. Macroscopic examination of the specimen showed compartmentation in the lesions, and microscopically, the lesions all showed lining of cubic or columnar epithelium on the inner wall with ovary-like or fibrous stroma. Complete resection of the tumor was achieved in 8 cases and partial resection was performed in 2 cases. The patients were followed up for a mean of 55.3 (12-164) months, and none of the patients with complete tumor resection showed recurrence, while both of the two patients with partial resection had postoperative recurrence.</p><p><b>CONCLUSION</b>IBCA is a rare cystic lesion occurring primarily in middle-aged women. The preoperative diagnosis of this disease relies primarily on radiological evidences, and a complete resection of IBCA may prolong the patient survival.</p>

Association between polymorphism of BDNF and internalizing disorders / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the genetic association between brain-derived neurotrophic factor (BDNF) gene polymorphism and internalizing disorders, to provide the theoretical basis to explore the etiology of internalizing disorders.</p><p><b>METHODS</b>PCR-based ligase detection reaction (PCR-LDR) was applied to tag single nucleotide lengh polymorphism (SNPs) of BDNF gene among 259 undergraduates affected by internalizing disorders and 269 healthy undergraduates. Haplotype analysis and multiple locus analysis were conducted to analyze the genotyping data.</p><p><b>RESULTS</b>The genotypic frequency of tag SNPs of BDNF gene did not deviate from Hardy-Weinberg equilibrium in both case and control groups. Rs12273539 was not associated with internalizing disorders (P > 0.05), but rs10835210 and rs2030324 were related to internalizing disorders (P < 0.05). The case group had more A allele of rs10835210 and C allele of rs2030324 when compared to the controls while A allele of rs10835210 and C allele of rs2030324 seemed to be the risk factors of internalizing disorder (OR = 1.877, P < 0.001; OR = 1.347, P < 0.05). Results of multiple locus analysis showed that the haplotype composed by the three tag SNPs which was related to internalizing disorders (chi(2) = 23.537, P < 0.001).</p><p><b>CONCLUSION</b>BDNF gene might serve as the susceptible gene for internalizing disorder.</p>

Study on the genetic association between the polymorphism of cytosolic phospholipase A2 family genes and schizophrenia / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the genetic association between the polymorphism of cytosolic phospholipase A2 (cPLA2) family genes and schizophrenia in the North Han Chinese.</p><p><b>METHODS</b>Method of polymerase chain reaction-based ligase detection reaction (PCR-LDR) was applied to genotype 10 single nucleotide polymorphisms (SNPs) of cPLA2 family genes among 201 pedigrees consisting of fathers, mothers and affected offsprings with schizophrenia. Haplotype relative risk (HRR) test, transmission disequilibrium test (TDT), haplotype transmission analysis and multiple locus analysis were conducted to analyze the genotyping data.</p><p><b>RESULTS</b>The genotypic frequency of cPLA2 gene did not deviate from Hardy-Weinberg equilibrium in both case and control groups. HRR and TDT showed that the 10 SNPs were not associated with schizophrenia (P > 0.05). Analysis for haplotype transmission showed that no haplotype systems was associated with schizophrenia (P > 0.05). Results from COA and COG tests showed a disease association for the rs2162886-rs1668589, rs891014-rs1668589 and rs2307279-rs7542180 combinations (chi2 = 6.913, P = 0.032; chi2 = 8.393, P = 0.015; chi2 = 8.447, P = 0.038).</p><p><b>CONCLUSION</b>Many loci in the cPLA2 family genes were associated with schizophrenic.</p>

Surgical treatment of 402 consecutive cases for hilar cholangiocarcinoma: Chinese single center experience / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze clinical typing, pathologic characteristics of hilar cholangiocarcinoma (HCCA) and surgical strategies and their effects on HCCA, and to explore the factors that influence the surgical outcomes and long-term survival.</p><p><b>METHODS</b>The data of the 402 patients with HCCA admitted between January 1993 and December 2004 was investigated retrospectively. Primary outcomes examined included clinical typing, pathologic characteristics, surgical procedures and follow-up results. On the basis of Bismuth-Corlette typing, we defined the tumor originated from intrahepatic large bile duct (LBD) as type V (type Va and Vb).</p><p><b>RESULTS</b>Among the 402 patients with HCCA, 198 cases accepted curative resection, 102 (51.5%) for radical resection and 96 (48.5%) for palliative resection. Of the rest patients, 8 received orthotopic liver transplantation (OLT), 161 received simple drainage and 35 were not operated on. The resection rates for type I, II, IIIa, IIIb, IV, Va and Vb were 69.4%, 55.5%, 57.4%, 71.7%, 19.6%, 100% and 34.6%, respectively. The one-year survival rates for radical resection, palliative resection, simple drainage and untreated were 80.3%, 53.2%, 26.7% and 9.8%, respectively. And the three-year and five-year survival rates in the four groups were 41.9% and 33.3%, 19.6% and 14.7%, 3.3% and 0, 0 and 0, respectively. Significant difference was found in survival rates between the radical and palliative resection. In the patients who received tumor resection, the ones without lymph nodes metastasis (LNM) survived much longer than those with LNM (P < 0.05). Complications were found in 36.1% of the patients and the mortality rate was 0.3%.</p><p><b>CONCLUSIONS</b>HCCA type V originated from intrahepatic LBD has higher resection rate and better prognosis. The tumor differentiation is significantly correlated with the prognosis after operation. With HCCA, resection is still the major treatment selection. Curative resection carries the best effect. Extended radical resection of liver lobes, blood vessels, lymph nodes can prolong survive. The problem of high recurrence rate after OLT for HCCA has not been solved yet.</p>