Objective To evaluate the ultrasound (US) features of the encapsulated papillary thyroid carcinoma (EPTC). Methods From January 2005 to October 2009, ultrasonographic retrospective analysis was done on 33 cases of EPTC in Shanxi Province Tumor Hospital. Based on ultrasonographic features including shape, size, border, echogenicity, hypoechoic halo and microcalcification, 33 cases of EPTC were classified into two groups: 21 cases in irregular shape group and 12 cases in spherical or oval shape group. Results EPTC in the irregular shape group showed some ultrasonographic features including jagged border, irregular tumor shape and marked hypoechogenicity, while the ultrasonographic features of EPTC in the spherical or oval shape group included smooth border, regular shape, isoechogenicity and hypoechoic halo. Hypoechoic halo and isoechogenicity were found more frequently in EPTC of spherical or oval shape group than those in EPTC of irregular shape group. The size of EPTC in the spherical or oval group was commonly larger than that of EPTC in the irregular shape group. Conclusions The findings indicate that EPTC have some ultrasonographic features similar to benign follicular thyroid tumors.

OBJECTIVETo investigate the incidence and clinical features of mixed infections in children with Mycoplasma pneumoniae (MP) pneumonia.

METHODA total of 201 cases diagnosed as MP pneumonia were investigated for mixed infections by sputum bacterial culture, respiratory virus antigen detection and serum Chlamydia pneumoniae antibody test. For those with the indications for bronchoscopy, we also did bronchoalveolar lavage and lavage bacterial culture.

RESULTA high incidence (103/201, 51.2%) of mixed infections in children with MP pneumonia was revealed. The most frequent co-infected pathogen was Chlamydia pneumoniae (52, 25.9%), followed by viruses (29, 14.4%), and bacteria (22, 10.9%). Among viruses, respiratory syncytial virus was the most common (17, 8.5%), followed by adenovirus (6, 3.0%), parainfluenza virus type III (4, 2.0%) and influenza virus type B (2, 1.0%). Sputum bacterial culture was positive in 14/201 (7.0%) cases, Streptococcus pneumonia being most common (6, 3.0%). BALF culture yielded positive results in 11.6% (8/69), Streptococcus pneumonia was also common (5, 7.3%). Among 29 cases with MP and virus coinfection, 26 were younger than 3 years (89.7%), while for MP and Chlamydia pneumoniae coinfection, most of them were older than 3 years (40/52, 76.9%). Compared with non-mixed infections, those with mixed infections had longer fever duration (24.5% and 40.8% longer than 10 d), more frequently developed pleural effusion (11.2%, 23.3%) and large area of shadow in chest imaging (35.7%, 51.5%). White blood cell [(14.28 ± 4.99) × 10(9)/L], C-reactive protein (CRP) [69(32.5 - 99.5) mg/L] and neutrophil ratio in BALF [0.86 (0.63 - 0.91)] were much higher in children with mixed bacterial infections than that in non-mixed infections [(9.06 ± 3.47) × 10(9)/L, 3 (0 - 31.0) mg/L, 0.44 (0.03 - 0.88)]. But no significant difference was found in peripheral blood neutrophil proportion between mixed bacterial infections (0.38 ± 0.25) and non-mixed infections (0.51 ± 0.19).

CONCLUSIONMore than half of cases with MP pneumonia had mixed infections, most commonly caused by Chlamydia pneumonia followed by viruses. The incidence of mixed infections with bacteria was low. Mixed infections with virus were more common in young children, while mixed infection with Chlamydia pneumoniae was more common in older ones. Bacterial infections should be paid more attention, especially those caused by Streptococcus pneumoniae, for those with high peripheral white blood cell counts, high CRP levels and high proportion of neutrophils in BALF.

Adolescent ; Child ; Child, Preschool ; Chlamydophila pneumoniae ; isolation & purification ; Coinfection ; Female ; Humans ; Infant ; Inpatients ; Male ; Mycoplasma pneumoniae ; isolation & purification ; Pneumonia, Mycoplasma ; diagnosis ; microbiology ; virology ; Pneumonia, Viral ; diagnosis ; Respiratory Syncytial Viruses ; isolation & purification

OBJECTIVETo study the effects of angiotensin II receptor blockers (ARB), losartan and irbesartan, on blood pressure and serum uric acid (SUA) level in mild to moderate essential hypertensive patients complicating hyperuricaemia.

METHODSA total of 351 eligible patients were recruited in this multi-center, randomized, double-blind parallel clinical trial. After 1 week screening and a 2 week single-blinded placebo wash-out period, patients were randomly assigned to receive losartan 50 mg (n=76) or irbesartan 150 mg (n=175) once daily for 4 weeks, followed by a double-dose for another 4 weeks in patients whose seated DBP were >or=90 mm Hg or SBP>or=140 mm Hg at the end of 4 weeks. The SUA concentration and blood pressure were measured at baseline, 4 and 8 weeks post therapy.

RESULTSThree hundred and twenty-five patients completed the study (162 in the losartan group and 163 in the irbesartan group). Both groups were well matched for baseline clinical characteristics and demographics. SUA was significant reduced in losartan group (430.93 micromol/L vs 372.35 micromol/L, P<0.0001), but not in Irbesartan group (430.46 micromol/L vs 420.67 micromol/L, P>0.05) 8 weeks post therapy compared to baseline level. Blood pressure was significantly and equally reduced in both groups after 8 weeks treatment compared to baseline level (P<0.0001).

CONCLUSIONLosartan is an optimum choice of medication for patients with mild-to-moderate hypertension complicating hyperuricemia.

Adult ; Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Biphenyl Compounds ; therapeutic use ; Double-Blind Method ; Female ; Follow-Up Studies ; Humans ; Hypertension ; drug therapy ; metabolism ; Losartan ; therapeutic use ; Male ; Middle Aged ; Tetrazoles ; therapeutic use ; Uric Acid ; metabolism

To determine the efficacy and tolerance to cyclosporine A (CsA) based therapy in patients with myelodysplastic syndrome (MDS), 16 patients with MDS consisting of 10 refractory anemia (RA) and 6 refractory anemia with accessory blasts less than 10% (RAEB-1) were analyzed. Five patients had hypocellular bone marrows and 11 patients had normocellular or hypercellular marrows. The dose of CsA was 2.5-5.5 mg/(kg.d) for 2 weeks to 2 years (mean 8 months). Two out of 16 patients were treated with CsA alone, 14 patients were treated with CsA, recombinant human erythropoietin, androgens, 1, 25 dihydroxy vitamin D(3) or two or three of them combination with CsA. Treatment responses were classified according to the International Working Group (IWG) criteria as complete remission (CR), partial remission (PR), hematological improvement (HI) and no response (NR). Patients who obtained CR, PR or HI were defined as responders. The results showed that HI was observed in 12 patients, PR in 2 patients and NR in 2 patients. Total response rate was 87.5%. Response rates shown in neutrophil lineage, platelet and erythroid lineage were 83.3%, 66.7% and 60%, respectively; their shortest time required to obtain some hematologic improvement after initiation of CsA therapy was 2 weeks, 1 month and 1 month, respectively. Of 13 patients being transfusion-dependent before treatment, 3 patients did not need transfusion any more and 5 showed the reduced transfusion requirements after CsA therapy. In 10 patients with RA, 9 responded to CsA. Of 6 patients with RAEB, 1 patient had no response and died of RAEB-t and 5 patients had transient responses. One of the latter transformed to CMML and two relapsed. The total response rate decreased to 50% in the patients with CsA therapy lasting more than 3 months at the end of following-up. The adverse effects included hirsutism, hyperplastic gingiva, reversible hepatic and renal dysfunction. In conclusion, the usefulness of CsA based therapy for MDS-RA and RAEB-1 with any marrow cellularity is useful, the CsA dose of 3-5 mg/(kg.d) is safe and efficacious.
Adolescent ; Adult ; Aged ; Androgens ; administration & dosage ; Anemia, Refractory ; drug therapy ; Anemia, Refractory, with Excess of Blasts ; drug therapy ; Calcitriol ; administration & dosage ; therapeutic use ; Cyclosporine ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Erythropoietin ; administration & dosage ; therapeutic use ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Myelodysplastic Syndromes ; drug therapy ; Recombinant Proteins ; Treatment Outcome

OBJECTIVETo explore the distribution laws of TCM syndrome types and to analyze the distribution of dynamic blood pressure curve, atherosclerosis, and age in senile hypertension patients.

METHODSTotally 1 131 senile hypertension patients were recruited from 7 provinces and municipal cities. Features of TCM syndromes, classification and distribution curves, and syndrome distribution laws were observed. The distribution curves of dynamic blood pressure, carotid atherosclerosis, and age were compared in each TCM syndrome types.

RESULTSThere were four main syndrome types in 736 cases (56.15%), i.e., excessive accumulation of phlegm-dampness syndrome (210 cases, 16.02%), yin deficiency and hyperactivity of yang syndrome (177 cases, 13.50%), Gan-Shen yin deficiency syndrome (79 cases, 6.03%), and deficiency of qi and yin syndrome (252 cases, 19.22%). Besides, there were two more sub-types, i.e., collateral obstruction by blood stasis syndrome and collateral obstruction by phlegm and stasis. Circadian blood pressure monitor was completed in 211 cases. Of them, abnormal circadian blood pressure occurred in 152 cases (accounting for 72. 38%); yin deficiency and hyperactivity of yang syndrome, excessive accumulation of phlegm-dampness syndrome, deficiency of qi and yin syndrome plus collateral obstruction by blood stasis syndrome were most often seen. Color ultrasound of carotid artery was performed in 660 patients of main syndromes. The incidence was quite higher in those of excessive accumulation of phlegm-dampness syndrome (182 cases, 27. 58%), deficiency of qi and yin syndrome plus collateral obstruction by blood stasis syndrome or collateral obstruction by phlegm and stasis (322 cases, 48.79%). Yin deficiency and hyperactivity of yang syndrome was dominant in patients 60 -79 years old, while deficiency of qi and yin syndrome and Gan-Shen yin deficiency syndrome were dominant in patients older than 80 years.

CONCLUSIONSExcessive accumulation of phlegm-dampness syndrome, yin deficiency and hyperactivity of yang syndrome, Gan-Shen yin deficiency syndrome, and deficiency of qi and yin syndrome were main syndrome types in senile hypertension patients. There was statistical difference in the distribution curves of blood pressure, atherosclerosis, and age of various TCM syndrome types.

Aged ; Asian Continental Ancestry Group ; Atherosclerosis ; epidemiology ; Biomedical Research ; Blood Pressure ; Humans ; Hypertension ; epidemiology ; Medicine, Chinese Traditional ; Qi ; Research Design ; Risk Factors ; Yin Deficiency ; epidemiology

Objective To investigate the relationship between blood pressure variability (BPV) and left ventricular diastolic function in patients with essential hypertension.Methods Left ventricular diastolic function of 252 hypertensive patients were assessed by early (E) diastolic transmitral flows to early diastolic mitral annular velocity (Ea) (E/Ea) ratio derived from Doppler echocardiography.Patients were divided into two groups according to normal left ventricular diastolic function group (E/Ea ＜ 15,n =168) and left ventricular diastolic dysfunction group (E/Ea ≥ 15,n =84).All patients were monitored by ambulatory blood pressure.Standard deviation (SD) and coefficient of variation (CV) of blood pressure were calculated as the BPV.Relationship between BPV and left ventricular diastolic function were analyzed by multivariate logistic regression analysis.Results All-day average diastolic blood pressure(DBP),the day systolic blood pressure (SBP),night SBP,night DBP,SBPSD,DBPSD and DBPCV in the left ventricular diastolic dysfunction group were significantly higher than in the normal diastolic function group (all P ＜ 0.05).Multivariate logistic regression analysis showed that left ventricular diastolic dysfunction was associated with SBPSD (OR:1.126,95 ％ CI:1.054-1.203,P ＜ 0.01),SBPCV (OR:1.127,95 ％ CI:1.036-1.225,P ＜ 0.01) in this patient cohort.Conclusion High variability of SBP is correlated with left ventricular diastolic dysfunction in hypertensive patients.

OBJECTIVETo investigate the efficacy of continuous propofol infusion via the common carotid artery for general anesthesia.

METHODSForty adult patients scheduled for abdominal surgery were randomly assigned into 2 groups to receive propopol via the common carotid artery (IC group, n=20) or via the median cubital vein (IV group, n=20). Anesthesia was induced with intravenous administration of drugs and maintained with continuous propofol infusion via the common carotid artery or the median cubital vein, with the CSI stabilized at 40-/+5 till the end of the operation. During the anesthesia, intravenous injection of fentanyl (3 microg.kg(-1).h(-1)) and vecuronium (50 microg.kg(-1).h(-1)) were given intermittently to maintain the analgesia and muscular relaxation. The dose of propofol used, hemodynamics and recovery of the patients were observed.

RESULTSThe dose of propofol used during the surgery to maintain a CSI of 40-/+5 was significantly lower in group IC and than in group IV (2.57-/+0.67 vs 5.72-/+1.37 mg.kg(-1).h(-1), P<0.01). In group IC, the blood pressure was elevated in more than half of the patients and in some cases, the elevation exceeded one third of baseline value and needed intervention with hypotensive drugs. In the IV group, the patients' blood pressure remained stable and varied within the amplitude of 15% of the baseline level. Recovery of spontaneous breathing and consciousness was more quickly in group IC than in group IV (P<0.05).

CONCLUSIONLoss of consciousness and nervous reflex can be achieved with propofol infusion via the common carotid artery, which reduces propofol dose by about 50% in comparison with intravenous infusion and allows more rapid recovery of spontaneous breath and consciousness.

Abdomen ; surgery ; Adult ; Aged ; Analgesics, Opioid ; administration & dosage ; Anesthesia, General ; methods ; Carotid Artery, Common ; Female ; Fentanyl ; administration & dosage ; Humans ; Hypnotics and Sedatives ; administration & dosage ; Infusions, Intra-Arterial ; Male ; Middle Aged ; Nicotinic Antagonists ; administration & dosage ; Propofol ; administration & dosage ; Treatment Outcome ; Vecuronium Bromide ; administration & dosage

Quantitative systems pharmacology (QSP) modeling is an emerging computational medicine approach with growing applications and significance in modern drug development. QSP models are generally formulated based on multiscale disease mechanisms and drug-target interactions, which makes them capable of integrating multimodal data from the preclinical and clinical space. This also enables them to generate quantitative characterization of the dynamic disease progression as well as high-throughput predictions of drug-induced efficacy and toxicity signals. Therefore, QSP modeling and model-based virtual clinical trials have been widely implemented to guide drug development, in scenarios such as target identification and assessment, clinical trial design, evaluation of combination therapy and biomarkers, and personalized medicine. In US and Europe, QSP modeling has been developing rapidly in the past 10 years and is now an integral part of the model-informed drug development paradigm; however, in China it is still a nascent field. Here we will present a comprehensive review of the recent advancements of QSP and its impact in modern drug development through a number of case studies. This review will provide guidance for the future drug development efforts and the growth of QSP practice in China.

Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/β-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knock-down.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/β-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alle-viated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.

OBJECTIVETo detect the JAK2, CALR and MPL gene mutations in patients with BCR/ABL1 negative chronic myeloproliferative diseases（BCR/ABL1-CMPD）and to evaluate their diagnostic value.

METHODSTwo hundred and eight cases of BCR/ABL1-CMPD comprising of 146 cases of essential thrombocythemia（ET）, 37 cases of polycythemia vera（PV）and 25 cases of primary myelofibrosis（PMF）from March 2012 to December 2015 were enrolled in the BCR/ABL1-CMPD, while 124 cases of secondary thrombocythemia and 73 cases of secondary polycythemia were enrolled in the control group. The genomic DNA and total RNA Were isolated from bone marrow or peripheral blood, then the exons 12 to 20 of JAK2 gene, exon 10 of MPL gene and exons 3 to 9 of CALR gene were analyzed by using DNA sequencing.

RESULTSamong 146 ET patients, the JAK2, CALR or MPL mutations were found in: 138 cases（94.5%）including 86 cases with JAK2V617F mutation（58.9%）and 2 cases（1.4%）with exon 12 of JAK2 mutations. CALR mutations were detected in 41 cases（28.1%）, among them type 1（c.1092_1143del）in 22 cases, type 2（c.1154_1155insTTGTC）in 11 cases, and type 5（c. 1091_1142del）, type 8（c.1104_1137del）, type 41(c.1107_1137del）, type 42(c.1125_1125del）in one case respectively. In addition, 4 cases were detected withother mutations of the CALR gene（c.1107_1115del, c.1111_1144 del, c.1101 A>C, c.1112_1117del）. Moreover, 9 cases harbored MPL mutations（6.2%）. Secondly, 31 patients were detected with JAK2V617F mutation（83.8%）in 37 cases of PV, and JAK2 exon 12 mutations were found in 2 cases（5.4%）. Besides, CALR mutations were detected in 2 cases（5.4%）, including 1 case of type I, the other of novel mutation of CALR. Thirdly, 19 in 25 cases of PMF were detected with JAK2V617F mutation（76%）, 2 cases with CALR mutations（8%）. 4 patients（16%）, JAK2, CALR or MPL mutations were not detected, but among them 3 cases were found harboring other genetic abnormalities. Fourthly, no mutations of JAK2, MPL and CALR genes were detected in 124 patients with secondary thrombocytosis and 73 cases with secondary polycythemia.

CONCLUSIONCombined detection of JAK2, CALR and MPL gene mutations can cover the vast majority of patients with BCR/ABL1-negative myeloproliferative neoplasms. For higher frequencies of the mutations of CALR in ET patients, CALR mutation can be used as a new diagnostic marker in ET patients with JAK2 and MPL wild type.

Calreticulin ; Humans ; Janus Kinase 2 ; Mutation ; Myeloproliferative Disorders ; Polycythemia Vera ; Receptors, Thrombopoietin ; Thrombocythemia, Essential