Animals ; Cardiomegaly ; Constriction ; Heart ; Mice

BACKGROUNDFamilial hypercholesterolemia (FH) is a type of dominant autosomal disease that causes high levels of plasma low-density lipoprotein cholesterol (LDL-C). In the past years, molecular data related to FH were limited in China. Now, to gain more information about FH, we analyzed one proband with a severe FH phenotype as well as his relatives.

METHODSAfter the entire coding sequence and the intron-exon junctions of the low-density lipoprotein receptor (LDLR) gene were amplified using PCR, we sequenced the LDLR gene of a Chinese FH family. RT-PCR was used to detect changes in the mRNA.

RESULTSTwo novel mutations were identified in the LDLR gene of this family. One, W165X, was a G > A substitution at the third nucleotide of codon 165. The other, IVS5-1G > A, was also a G > A substitution at the acceptor splice site of intron 5. The most striking discovery is that the proband was heterozygous for W165X but homozygous for IVS5-1G > A. The cDNA sequencing showed that the IVS5-1G > A mutation caused the insertion of 10 nucleotides, namely GCTCTCACAA, between exon 5 and exon 6.

CONCLUSIONSThe two nucleotide variations are thought to be the FH-causing mutations because the co-segregation of the mutant allele with the phenotype of FH has been shown in this Chinese family. These data show an increase in the mutational spectrum of FH in China and verify a scarce mutational form in the LDLR gene.

Adult ; Child ; DNA, Complementary ; analysis ; Female ; Humans ; Hyperlipoproteinemia Type II ; genetics ; Male ; Mutation ; Pedigree ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Receptors, LDL ; genetics

OBJECTIVETo improve the diagnosis and treatment of far advanced prostate cancer without clinically detectable bone metastasis.

METHODSCancer metastatic lesions were found in the liver and lungs respectively of two patients on routine medical examination, and only an abnormally elevated level of the serum prostate specific antigen (PSA) was observed in the following system examinations. The patients were diagnosed as having prostate cancer by prostate biopsy. MRI showed a discontinued prostate capsule, and ECT revealed no bone metastasis. Diagnostic treatment was conducted by giving LHRHa combined with antiandrogens. One of the patients underwent surgical castration at 12 months, and both received intensity modulated radiation therapy (80 Gy) at 15 and 18 months, respectively.

RESULTSThe metastatic lesions in the liver and lungs of the patients were either absent or significantly reduced after treated by maximal androgen blockade for 3 months, and all disappeared after 6 months'treatment, with the PSA level stabilized at less than 0.02 microg/L in one patient, and around 0.5 microg/L in the other. Antiandrogen treatment was suspended after radiotherapy. The results of liver, lung and bone scanning were normal during the 12-month follow-up, and the PSA level was below 1.0 microg/L.

CONCLUSIONRemote metastasis of prostate cancer may occur in ectosteal organs first, which deserves special attention. A combination of different treatment methods promises satisfactory results.

Aged ; Humans ; Liver Neoplasms ; secondary ; Lung Neoplasms ; secondary ; Male ; Neoplasm Metastasis ; Prostatic Neoplasms ; diagnosis ; pathology ; therapy

OBJECTIVETo study the endogenous hormone of testosterone and cortisol that secretes volume and rhythm in sports fatigued human bodies and animals. To determine secretory volume and rhythm in sports fatigued human bodies and animals when Shixiang yaofa's drug are used.

METHODRadio-immunity method was used to determine secretory volume and rhythm in sports fatigued human bodies and animals and to analyze secretory volume and rhythm. According to the secretory volume and rhythm of testosterone and cortisol, the Shixiang Yaofa's drugs were used. Doses: wenyang jihuo bead 10 g/sack 2 sack, ziyin xiuyang capsule 0.5 g/pill 8 pill pd in human bodies for 28 days. Wenyang jihuo bead 10 g x kg(-1) of crude drug, ziyin xiuyang capsule 4 g x kg(-1) of crude drug pd for hight doses in animals. Other groups for low doses 5 g x kg(-1) and 2 g x kg(-1) of crude drug pd for 15 days. The blood samples were collected for determination.

RESULT(1) In human bodies the peak value of testosterone was appeared in 8:00 and valley value was appeared in 18:00, ranges: 176.93-281.73 x 10(-5) mg x L(-1). The peak value of cortisol was appeared in 8:00 and valley value was appeared in 22:00, ranges: 1.31-16.13 x 10(-3) mg x L(-1). In the same condition, the mouse peak value of testosterone was appeared in 20:00 and valley value was appeared in 0:00, ranges: (0.56 x 10(-5) - 124.0 x 10(-5)) mg x L(-1). The rhythm in animals was compatible with human bodies, howerer, the peak value was delayed for 12 hours. (2) The testosterone was step up and the cortisol was cut down in sports fatigued human bodies and animals when shixiang yaofa's drug were used (P < 0.05, P < 0.01).

CONCLUSIONThe secretion of testosterone and cortisol in sports fatigued human bodies and animals are existed conclusive biologic rhythm. The secretory volume can be available accommodation by shixiang yaofa's drugs.

Adolescent ; Adult ; Animals ; Chronotherapy ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Fatigue ; etiology ; physiopathology ; Female ; Humans ; Hydrocortisone ; secretion ; Male ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred ICR ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sports ; Testosterone ; secretion

OBJECTIVESOrthotopic liver transplantation (OLT) is an accepted therapy for selected patients with advanced liver diseases. However, the early mortality rate after OLT remains relatively high due to the poor selection of candidates with various serious conditions. The aim of this study is to assess the value of pretransplantation artificial liver support treatment in reducing the pre-operation risk factors relating to early mortality after OLT.

METHODS50 adult patients in various stages of different etiologies who underwent OLT procedures had been treated with molecular adsorbent recycling system (MARS) preoperatively. The study was designed in two parts: the first one was to evaluate the effectiveness of a single MARS therapy by using some clinical and laboratory parameters which were supposed to be therapeutical pretransplantation risk factors. The second part was to study the patients undergoing OLT by using the regression analysis on preoperation risk factors relating to early (within 30 d after OLT) mortality rate.

RESULTSAmong the 50 patients, a statistically significant improvement of the biochemical parameters was observed (pretreatment vs posttreatment). 8 patients cancelled their scheduled LTXs due to significant improvements in their clinical conditions or recovery of their failing liver functions. 8 patients died and 34 patients successfully underwent LTX. The immediate outcome (within 30 postoperative days) of these 34 patients was that 28 were kept alive and 6 died.

CONCLUSIONSPreoperation sequential organ failure assessment (SOFA), level of creatinine, INR, TNFalpha, and IL-10 are the main preoperative risk factors relating to early death after an operation. MARS treatment before a transplant operation can relieve these factors significantly, hence improve survival rate of liver transplantation or even make the transplantation unnecessary.

Aged ; Factor Analysis, Statistical ; Female ; Humans ; Interleukin-10 ; blood ; Liver Cirrhosis ; surgery ; Liver Neoplasms ; surgery ; Liver Transplantation ; methods ; Liver, Artificial ; Male ; Middle Aged ; Preoperative Care ; Risk Factors ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVEAn accurate clinical TNM staging of lung cancer is essential for the precise determination of the extent of the disease in order that an optimal therapeutic strategy can be planned. This is especially true in patients with marginally resectable tumors. Clinical over-staging of the disease may deny a patient the benefit of surgery, whereas under-staging may oblige a patient to accept a fruitless or even harmful surgery. We aimed to analyze preoperative clinical (c-TNM) and postoperative surgico-pathologic staging (p-TNM) of lung cancer patients in order to evaluate the accuracy of our clinical staging and its implications on the surgical strategy for lung cancer.

METHODSWe did a retrospective comparison of c-TNM and p-TNM staging of 2007 patients with lung cancer surgically treated from January 1999 to May 2003. Preoperative evaluation and c-TNM staging of all patients were based on physical examination, laboratory studies, routine chest X-ray and CT scan of the chest and upper abdomen. Other examinations included sputum cytology, bronchoscopy, abdominal ultrasonography, bone scintiscan, brain CT/MRI, and mediastinoscopy whenever indicated.

RESULTSIn the present study the comparison of c-TNM and p-TNM staging of 2007 patients with lung cancer revealed an overall concurrence rate of only 39.0%. In the entire series the extent of disease was clinically underestimated in 45.2% and overestimated in 15.8% of the patients. Among all c-TNM stages the c-IA/B stage of 1105 patients gave the highest rate (55.2%) of underestimating the extent of disease. Clinical staging of T subsets was relatively easy with an overall accuracy rate of 72.9%, while that of N subsets was relatively more difficult with an overall accuracy rate of 53.5%. Analysis also showed that c-IV stage may not be an absolute contraindication to surgery, because in half of the patients, c-M1 turned out to be p-M0, providing the possibility of resectional surgery depending on the status of T and N.

CONCLUSIONFor reasons to be further determined, the present preoperative clinical TNM staging of lung cancer remains a crude evaluation. Further efforts to improve its accuracy are needed.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; pathology ; surgery ; Female ; Humans ; Lung Neoplasms ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Pneumonectomy ; Retrospective Studies

In this study, the underlying mechanism of Qiwei Guibao Granules(QWGB) in the treatment of premature ovarian fai-lure(POF) was explored by the proteomics technique. Firstly, the POF model was induced in mice by intragastric administration of Tripterygium wilfordii glycosides solution at 50 mg·kg~(-1) for 14 days. Ten days prior to the end of the modeling, the estrous cycle of mice was observed every day to evaluate the success of modeling. From the 1st day after modeling, the POF model mice were treated with QWGB by gavage every day and the treatment lasted four weeks. On the 2nd day after the end of the experiment, blood was collected from the eyeballs and the serum was separated by centrifugation. The ovaries and uterus were collected and the adipose tissues were carefully stripped. The organ indexes of the ovaries and uterus of each group were calculated. The serum estrogen(E_2) level of mice in each group was detected by ELISA. Protein samples were extracted from ovarian tissues of mice, and the differential proteins before and after QWGB intervention and before and after modeling were analyzed by quantitative proteomics using tandem mass tags(TMT). As revealed by the analysis of differential proteins, QWGB could regulate 26 differentially expressed proteins related to the POF model induced by T. wilfordii glycosides, including S100A4, STAR, adrenodoxin oxidoreductase, XAF1, and PBXIP1. GO enrichment results showed that the 26 differential proteins were mainly enriched in biological processes and cellular components. The results of KEGG enrichment showed that those differential proteins were involved in signaling pathways such as completion and coalescence cascades, focal adhesion, arginine biosynthesis, and terpenoid backbone biosynthesis. The complement and coalescence cascades signaling pathway was presumably the target pathway of QWGB in the treatment of POF. In this study, the proteomics technique was used to screen the differential proteins of QWGB in the treatment of POF in mice induced by T. wilfordii glycosides, and they were mainly involved in immune regulation, apoptosis regulation, complement and coagulation cascade reactions, cholesterol metabolism, and steroid hormone production, which may be the main mechanisms of QWGB in the treatment of POF.
Female ; Humans ; Mice ; Animals ; Primary Ovarian Insufficiency/chemically induced* ; Proteomics ; Signal Transduction ; Glycosides/adverse effects*

Cervical cancer (CC) is recognized as the most common neoplasm in the female reproductive system worldwide. The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients. Aloperine (ALO) is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation, allergies and infection. However, its therapeutic efficacy and underlying mechanism in CC are still unclear. In the current study, MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC. Then, the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry, respectively, while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay. Moreover, nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo. The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis. This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest. Simultaneously, ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio. Additionally, the migration and invasion of HeLa cells were attenuated by ALO treatment, which was considered to result from inhibition of epithelial-to-mesenchymal transition. For molecular mechanisms, the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment. This study indicated that ALO markedly suppresses the proliferation, migration and invasion and enhances the apoptosis of HeLa cells. In addition, these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.
Animals ; Apoptosis ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Feedback ; Female ; HeLa Cells ; Humans ; Interleukin-6/genetics* ; Janus Kinase 1 ; Mice ; Mice, Nude ; Quinolizidines ; STAT3 Transcription Factor/genetics* ; Signal Transduction ; Uterine Cervical Neoplasms/drug therapy*

Accurate methods for identifying pelvic lymph node metastasis (LNM) of prostate cancer (PCa) prior to surgery are still lacking. We aimed to investigate the predictive value of peripheral monocyte count (PMC) for LNM of PCa in this study. Two hundred and ninety-eight patients from three centers were divided into a training set (n = 125) and a validation set (n = 173). In the training set, the independent predictors of LNM were analyzed using univariate and multivariate logistic regression analyses, and the optimal cutoff value was calculated by the receiver operating characteristic (ROC) curve. The sensitivity and specificity of the optimal cutoff were authenticated in the validation cohort. Finally, a nomogram based on the PMC was constructed for predicting LNM. Multivariate analyses of the training cohort demonstrated that clinical T stage, preoperative Gleason score, and PMC were independent risk factors for LNM. The subsequent ROC analysis showed that the optimal cutoff value of PMC for diagnosing LNM was 0.405 × 109 l

Phyllanthi Fructus, a unique Chinese and Tibetan medicinal plant with both edible and medical values, has high potential of cultivation and development. The resources of Phyllanthi Fructus in China are rich, mainly distributed in Yunnan, Sichuan, Fujian, Guangdong, Guangxi, etc. Phyllanthi Fructus is widely used in the clinical practice of Chinese medicine and plays an important role in Tibetan medicine, Uyghur medicine, Yi medicine, and Mongolian medicine. Phyllanthi Fructus mainly contains phenolic acids,tannins, terpenes, sterols, fatty acids, flavonoids, amino acids and other compounds. Modern pharmacological studies show that Phyllanthi Fructus has antioxidant, anticancer, blood lipid-lowering, liver protective, antimicrobial, anti-inflammatory, and immune regulatory activities. In this paper, the research status of Phyllanthi Fructus was reviewed from the aspects of herbal textual research,chemical composition, and pharmacological action. The quality markers(Q-markers) of Phyllanthi Fructus were predicted and analyzed from the aspects of biogenic pathway, specificity and measurability of chemical components, efficacy, properties, new clinical uses, drug-food homology, and transformation of polyphenols. The results will provide a scientific basis for the quality control, quality evaluation, and standard formulation of Phyllanthi Fructus.
China ; Drugs, Chinese Herbal ; Fruit ; Medicine, Tibetan Traditional ; Quality Control