ObjectiveTo screen out the main targets and related signaling pathways of the herbal pair Cremastrae Pseudobulbus-Rhapontici Radix in treating breast cancer based on network pharmacology and verify their action mechanism in in vitro experiments. MethodThe main chemical components and related targets of Cremastrae Pseudobulbus-Rhapontici Radix were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and the target genes related to breast cancer from GeneCards. Following the screening of the common targets of Cremastrae Pseudobulbus-Rhapontici Radix and breast cancer using Venn， the Cremastrae Pseudobulbus-Rhapontici Radix-breast cancer network and protein-protein interaction （PPI） network were constructed. The effective targets were then subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analysis. The resulting outcomes were then verified by cell counting kit （CCK）-8 assay， flow cytometry， and Western blot. ResultThe screening yielded seven effective components and 61 targets of Cremastrae Pseudobulbus-Rhapontici Radix， among which 55 targets were involved in breast cancer. The GO analysis revealed 832 entries， which were mainly enriched in the biological processes. According to KEGG pathway enrichment analysis， 85 signaling pathways were obtained， including tumor suppressor p53， vascular endothelial growth factor （VEGF）， epidermal growth factor receptor （EGFR）， and phosphatidylinositol 3-kinase （PI3K）/protein kinase B（Akt）. It was verified in in vitro experiments that the alcohol extract of Cremastrae Pseudobulbus-Rhapontici Radix inhibited the proliferation of human breast cancer MDA-MB-231 cells and induced their apoptosis. Compared with the blank control group and the dimethyl sulfoxide （DMSO， 0.1% solvent） group， the medication groups exhibited obviously decreased absorbance in MDA-MB-231 cells （P<0.01） and increased apoptosis rate （P<0.01）. The results of Western blot demonstrated that compared with the blank control group and the DMSO group， each medication significantly reduced the phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in cells （P<0.05）. ConclusionThe ethanol extract of Cremastrae Pseudobulbus-Rhapontici Radix effectively inhibits the proliferation of human breast cancer MDA-MB-231 cells and induces their apoptosis， which may be related to the inhibition of the activation of PI3K/Akt signaling pathway.

Preoperative detection of biomarkers that can predict postoperative survival of gastric cancer patients has important implications for surgical procedures, postoperative chemoradiotherapy and followup. Using multi-center cancer database and online analysis and verifying by qRT-PCR and Western blotting, we found that Osteomodulin (OMD) was highly expressed in gastric cancer tissues (P =0. 015) and could affect the survival of gastric cancer patients (P < 0. 001) and can be detected preoperatively to evaluate the prognosis of gastric cancer patients. The mRNA expression of OMD was significantly correlated with age (P = 0. 034), Lauren typing (P < 0. 001) and clinical stage (P =0. 001) of gastric cancer patients. It also associated with a variety of immune cells (dendritic cellsresting, eosinophils) and the immune checkpoint regulator ENTPD1 (rho = 0. 634, P < 0. 001) and chemokine CXCL12 (rho = 0. 625, P < 0. 001), which affects the occurrence and development of gastriccancer through the immune microenvironment. Therefore, OMD may become a clinically feasible prognostic biomarker of gastric cancer and a new target for immunotherapy.

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
Acquired Immunodeficiency Syndrome/prevention & control* ; China/epidemiology* ; Disease Outbreaks ; HIV Infections/prevention & control* ; Humans ; Prevalence

Background/Aims: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. Methods: Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). Results: Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. Conclusions Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

[Objective]To investigate the feasibility of making the protocol with computed tomography data for total knee arthroplasty using patient-specific femoral and tibial cutting blocks.[Methods]54 consecutive patients diagnosed with osteoarthritis were divided randomly into two groups. Every patients accepted 3-dimentional computed tomography scan for bilateral legs before operation,the protocol were made for every patients before operation.When making the pre-operative protocol,we accepted the prothesis surpass the osteotomy edge finitely,tibia prothesis rotational orientation according to the outline of the tibial osteotomy. The thickness of the posterior condyle of femur resected was as the same with the prothesis posterior condyle as possible. The patients in trial group undergone total knee arthroplasty(TKA) using patient-specific instruments(PSI)according to the preoperative protocol,while the patients in the control group undergone TKA using custom instruments(CI).The operation time,the times that the scale of the prosthesis were altered intraoperation,the mean thickness of the posterior condyle of femur resected in the operation,AKS score 3 months and 1 year after the operation were recorded and compared between the two groups. Plain film radiography after the operation were analyzed.[Results]No significant differences were found between two groups with respect to the operation time. 8 patients altered to a lesser prosthesis in the CI group during the operation,all in bibia contrast to no one need alteration in the PSI group.The thickness of the osteotomy on the posterior condyle of femur in the PSI group is bigger than that of CI group as a result.The AKS score of the patients in the PSI group is higher than that of CI group 3 months after the opera-tion,whereas no significant difference was found 1 year after the operation.[Conclusion]The reconstructed image by thin layer CT can be used for preoperation protocol for TKA,which might be helpful in deciding the size of femour prosthesis;the implants can surpass the edge of the osteotomy finitely in TKA,which is not necessarily cause any complain.We can orient the tibia prosthesis rotation according to the outline of the osteotomy of the patients'tibia.

To understand the genetic diversity and drug resistance status of Mycobacterium tuberculosis (M. tuberculosis) circulating in Xuzhou of China, the spacer-oligonucleotide typing (Spoligotyping) and multi-loci VNTRs (variable number tandem repeats) analysis (MLVA) were utilized for the genotyping of the isolates. Drug susceptibility test (DST) was performed by the proportion method on the Lowenstein-Jensen (L-J) medium using isoniazid, rifampicin, ethambutol, and streptomycin. By Spoligotyping, 287 M. tuberculosis isolates were differentiated into 14 clusters. Then with 15-loci MLVA, these strains could be divided into 32 clusters, 228 genotypes. Of 15 VNTRs, 6 loci had the highly discriminatory powers, 6 loci presented moderate discrimination and 3 loci demonstrated less polymorphism. The DST results showed that 46 strains were resistant to at least one first-line anti-tuberculosis agent. There was a difference in the isoniazid resistance between Beijing and non-Beijing genotype strains. We concluded that the combination of Spoligotyping and 15 VNTR loci as the genotyping in our study was applicable for this region, the drug resistant isolates were identified, and the Beijing family was the most prevalent genotype in the rural counties of Xuzhou.
China ; Drug Resistance, Bacterial ; genetics ; Genotyping Techniques ; Mycobacterium tuberculosis ; genetics

OBJECTIVETo analyze and summarize the clinical characteristics, experience of diagnosis and treatment of cases infected by new bunyavirus, which occurred in Henan province in 2010.

METHODSThe clinical characteristics and effect of diagnosis and treatment of 5 cases were analyzed using descriptive epidemiological method. Blood specimens were detected by RT-PCR and pathogen separation.

RESULTSPCR testing was positive for all 5 cases. New bunyavirus were isolated from 2 cases. In 5 cases, fever (5/5), the whole body aches (5/5), fatigue (5/5), anorexia (5/5), nausea (5/5), the chills (4/5), cough (4/5), expectoration (4/5), vomiting (3/5), conjunctival hyperemia (3/5); Leukocyte reduction (5/5), thrombocytopenia (5/5), elevated alanine aminotransferase (4/5), elevated aspartate aminotransferase (4/5), elevated lactate dehydrogenase (5/5), creatine kinase elevations (4/5), urinary protein (3/5). By symptomatic and supportive treatment and prophylactic antibiotics, the first case died and the other 4 cases were cured. The average course of disease was 15.4 days.

CONCLUSIONCases infected by new bunyavirus have complicated clinical feature and multiple organ damage. If symptomatic treatment is in time, prognosis will be good.

Adult ; Bunyaviridae Infections ; diagnosis ; therapy ; virology ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Orthobunyavirus ; Prognosis ; Young Adult

ObjectiveTo analyze the expression of osteopontin (OPN) and interleukin-17 (IL-17)and study the roles in the pathogenesis of chronic severe hepatitis B.MethodsTwenty patients of acute on chronic liver failure were collected from the infection disease in-patients department of the First Affiliated Hospital of Medical College,Zhejiang University from 2009 to 2010,and 40 health controls were from medical examination center during the same period.Meanwhile,Balb/C mice were used for ConA injection to induce fulminant hepatitis and the plasma,serum and liver tissue of mice were collected.OPN and IL-17concentrations were measured using ELISA kits.PBMC were separated and cultured with anti-TNF-α or TNF-α.Supernatants were collected for analysis of OPN and IL-17.Differences between groups were evaluated by using a Student's t test and the relationship between IL-17 and OPN were evaluated by Pearson correlation.ResultsIn chronic severe hepatitis B group,levels of OPN and IL-17 were markedly higher than those of healthy control,respectively.(42.4 ± 12.9 vs 10.6 ±4.8 pg/ml; 1460.1 ±523.1 vs 472.8 ±67.5 ng/ml) ( t =2.387,3.570,P ＜ 0.05).The level of OPN in blood and liver reached peak at 6 hours at 12 hours after ConA injection,respectively.The level of IL-17 in blood and liver was significantly increased after ConA injection.IL-17 were positive correlated with OPN levels (R2 =0.582,P =0.026).TNF-α can increase the level of OPN secreted by lymphocytes.ConclusionsOPN and IL-17 levels in peripheral blood of hepatitis B patients are closely related to the hepatitis B degree.TNF-α can increase the level of OPN secreted by lymphocytes.

The aim of this study was to investigate the effect of integripetal rhodiola herb on pulmonary arterial remodeling and expression of vascular endothelial growth factor (VEGF) in high altitude pulmonary hypertension in rats. Fifty healthy male Wistar rats were divided into five groups randomly: Plain control group (LC group), 10-day plateau group (H(10) group), 30-day plateau group (H(30) group), 10-day rhodiola-treated plateau group (R(10) group), and 30-day rhodiola-treated plateau group (R(30) group). Each group included 10 rats. The rats in LC group were kept in Chengdu (500 meters above sea level), and rats in H and R groups were kept in Lhasa (3 700 meters above sea level). The rats in R group were daily treated with integripetal rhodiola herb extract (24%, 10 mL/kg) intragastrically for 10 d or 30 d, while rats in LC and H groups were treated with the same volume of saline. Mean pulmonary arterial pressure (mPAP) was detected via a catheter in the pulmonary artery by pressure waveform monitoring. The ratio value of right ventricle weight to left ventricle plus septum weight [RV/(LV + S)] was measured. The microstructure of pulmonary arterioles was examined by electron microscopy. The expression of VEGF in the lung was investigated using immunohistochemistry. The results showed that mPAP and [RV/(LV + S)] in H(10) group and H(30) group were higher than those in LC group (P < 0.05); but there was no significant difference between H(10) group and R(10) group (P < 0.05); and mPAP and [RV/(LV + S)] in H(30) group were lower than those in H(30) group (P < 0.05). Electron microscopy showed that compared to LC group, arteriolar endothelial cells were arranged in a columnar or palisading form, protruding into the lumen, accompanied with luminal stenosis, irregular internal elastic membrane, and proliferation of vascular smooth muscle cells in H groups, which was more obvious in H(30) group than in H(10) group; while these pathological changes were attenuated in the R groups compared to H groups. The levels of VEGF protein in H groups were also higher than those in LC group (P < 0.05); while the expression of VEGF in R(30) group was lower than that in H(30) group. In summary, the results show that the integripetal rhodiola herb can attenuate high altitude-induced pulmonary arterial remodeling in rats, and the inhibition of VEGF protein expression by rhodiola may be one of the mechanisms.
Altitude ; Altitude Sickness ; prevention & control ; Animals ; Arterioles ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Hypertension, Pulmonary ; metabolism ; pathology ; physiopathology ; Male ; Pulmonary Artery ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar ; Rhodiola ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVEMultiple genetic and environmental factors contribute to the onset of many human diseases, such as neonatal hyperbilirubinemia. OATP 1B1 is an important polymorphism gene which transmembrane transports unconjugated bilirubin(UCB). Genetic polymorphisms that affect the functionality of the protein may potentially lead to altered transport characteristics. The T521C/A388G polymorphism of this gene has been reported to considerably reduce the transporting property of drugs like pravastatin, and may be involved in the membrane translocation of bilirubin. Some studies have shown that OATP 1B1 mediates bilirubin uptake from blood into the liver, and the OATP 1B1 polymorphism is a likely mechanism explaining the differences of bilirubin level in peripheral blood. The aim of this study was to evaluate the relationship between OATP 1B1 polymorphisms and neonatal hyperbilirubinemia.

METHODSA total of 220 newborn infants with hyperbilirubinemia were recruited from Hunan Children Hospital from November 2008 to December 2009 according to the diagnostic criteria. Age and sex matched control subjects comprised of 200 unrelated, hyperbilirubinemia-free newborns. Biochemical and clinical data were collected from the case history. One ml venous blood samples in EDTA vials were taken from each subject and DNA was isolated from peripheral leukocytes by standard methods, preserved in 4°C. 1 - 2 ml venous blood samples were also taken for detecting the serum total bilirubin and direct bilirubin level by chemical oxidation method. OATP 1B1 T521C/A388G polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Allele and genotype frequencies were compared between patients and control. The gene polymorphism and risk of disease were also analyzed. Serum total bilirubin, conjugated bilirubin and unconjugated bilirubin levels were compared between different OATP 1B1 T521C/A388G genotypes.

RESULTSAllele frequencies in patients and control population were in Hardy-Weinberg equilibrium (P > 0.05). Allele and genotype frequencies of the OATP 1B1 T521C polymorphism in patients were significantly different from the controls. The OATP 1B1 521C allele frequency was only 8.2% in patients, while reached 14.0% in the control group which was very close to the frequency of common Chinese people. However, the proportion of wild type genotypes was significantly higher than those of the controls, reached 84.1%. The 521 C allele and genotypes carrying 521 C allele illustrated low risk for neonatal hyperbilirubinemia (OR = 0.530, 95%CI = 0.328 - 0.857; OR = 0.541, 95%CI = 0.344 - 0.851). However, the frequencies of alleles and genotypes of SLCO1B1 A388G did not differ significantly from those of the controls, and this polymorphism did not influence susceptibility to such disease. Among the three OATP 1B1 A388G genotypes, the level of total serum bilirubin (TSB), direct bilirubin (DB) and unconjugated bilirubin (UCB) were significantly different. Values of TSB, DB and UCB were the highest in wild type subjects, lower in heterozygotes, and the lowest in mutant homozygotes. TSB and UCB in patients with wild type genotypes reached 602.5 µmol/L and 585.0 µmol/L respectively, nearly twice the average value of homozygous patients. While the TSB and UCB in homozygotes were below the average value of all patients, only 351.7 µmol/L and 338.8 µmol/L respectively.

CONCLUSIONSOur findings indicated that OATP 1B1 A388G polymorphism has a notable influence on the serum bilirubin level in neonatal hyperbilirubinemia patients. The OATP 1B1 521T allele may be a potential risk factor of such disease. OATP 1B1 T521C/A388G was an important polymorphism gene which related with neonatal hyperbilirubinemia. Future study should involve other polymorphisms of OATP 1B1, more candidate genes and environmental risk factors. It is also necessary to investigate their association with the severity and prognosis of this disease in order to elucidate the genetic pathogenesis of neonatal hyperbilirubinemia as a complex disease. This study should be repeated in a larger population and different ethnic groups.

Bilirubin ; blood ; Case-Control Studies ; Female ; Humans ; Hyperbilirubinemia, Neonatal ; genetics ; Infant, Newborn ; Male ; Organic Anion Transporters ; genetics ; Polymorphism, Restriction Fragment Length ; Solute Carrier Organic Anion Transporter Family Member 1b1