Atherosclerosis caused by disorders of lipid metabolism is the main pathological basis of atherosclerotic cardiovascular disease.Statins are the cornerstone of lipid-modulating therapy for this type of disease,but in practice there are still some patients with suboptimal lipid management.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors have been gradually applied as a new class of lipid-modulating drugs for the treatment in patients with this type of disease,and recent studies have shown that in addition to regulating lipid metabolism,PCSK9 inhibitors also have potential anti-inflammatory and anti-platelet activation effects.This article sorts out the multiple pharmacological mechanisms of action of PCSK9 inhibitors and the current status of clinical research of PCSK9 inhibitors.Besides,it discusses the factors that may affect the efficacy of PCSK9 inhibitors,in order to provide a reference for the safe and rational medication of PCSK9 inhibitors.

Objective:To investigate the effect of metformin and arsenic trioxide on KG1a cells proliferation of acute myeloid leukemia and its possible mechanism.Methods:CCK-8 method was used to detect the killing effect of metformin,arsenic trioxide and combined application on KG1a cells.Annexin V-FITC/P1 Dual Stain Flow Cytometry was used to detect the effect of combined application on apoptosis of KG1 a cells.Western blot was used to detect the expression of intracellular apoptosis-,autophagy-related protein.Results:Metformin and arsenic trioxide alone or in combination could inhibit the proliferation of KG1 a cells and induce apoptosis of KG1 a cells,and the proliferation inhibition rate and apoptosis rate in the combined drug group were higher than those in the drug group alone(P＜0.05).The combination of drugs induced upregulation of Caspase 8 protein and P62 protein expression and was higher than that in the drug group alone(P＜0.05).Conclusion:Metformin can synergize with arsenic trioxide to kill KG1a cells,and its mechanism of action may be related to inducing apoptosis and enhancing autophagy.

Eleven compounds were isolated from the 95% ethanol extract of the stems of Dendrobium officinale after water extraction by various modern chromatographic techniques, such as silica gel column chromatography(CC), octadecyl-silica(ODS) CC, Sephadex LH-20 CC, preparative thin layer chromatography(PTLC) and preparative high performance liquid chromatography(PHPLC). According to spectroscopic analyses(MS, 1D-NMR, 2D-NMR) combined with optical rotation data and calculated electronic circular dichroism(ECD), their structures were identified as dendrocandin Y(1), 4,4'-dihydroxybibenzyl(2), 3-hydroxy-4',5-dimethoxybibenzyl(3), 3,3'-dihydroxy-5-methoxybibenzyl(4), 3-hydroxy-3',4',5-trimethoxybibenzyl(5), crepidatin(6), alternariol(7), 4-hydroxy-3-methoxypropiophenone(8), 3-hydroxy-4,5-dimethoxypropiophenone(9), auriculatum A(10) and hyperalcohol(11). Among them, compound 1 was a new bibenzyl derivative; compounds 2 and 7-11 have not been previously reported from Dendrobium plants; compound 6 was reported from D.officinale for the first time. Compounds 3-6 exhibited potent antioxidant activity with IC_(50) values of 3.11-9.05 μmol·L~(-1) in ABTS radical scavenging assay. Compound 4 showed significant inhibitory effect on α-glucosidase, with IC_(50) value of 17.42 μmol·L~(-1), indicating that it boasted hypoglycemic activity.
Dendrobium ; Biological Assay ; Chromatography, High Pressure Liquid ; Chromatography, Thin Layer ; Bibenzyls

Humans ; AIDS Dementia Complex/pathology* ; HIV Infections

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective:To evaluate the clinical efficacy and safety of Longmu Zhuanggu granule for the treatment of children recurrent respiratory infection due to lung-spleen Qi deficiency. Method:This multicenter stratified， block-randomized， double-blind， double-dummy， positive drug （pidotimod granule） parallel controlled， and non-inferiority trail intended to included 240 children patients and divided them into the experimental group （n=120） and the control group （n=120） at the ratio of 1∶1. Patients in both groups were treated for eight successive weeks and followed up for 12 months. The cure rates， numbers of respiratory infections， average courses of disease， curative effects of traditional Chinese medicine （TCM） syndrome， curative effects of individual symptoms， curative effects of immune indexes， and safety indexes between the two groups were observed and compared. Result:A total of 237 subjects were collected from 10 research centers， including 119 cases in the control group and 118 in the experimental group. There were 236 cases enrolled into the full analysis set （FAS）， 210 into the per-protocol set （PPS）， and 236 into the safety set （SS）. The baseline data of the two groups were not significantly different from each other， indicating that they were comparable. The cure rates of the experimental group and control group were 75.21% （88/117） and 73.95%（88/119）， respectively， with the 95% confidence interval （CI） of difference between the two groups being 1.26% （-9.85%，12.37%） for FAS and 3.81% （-6.28%，13.90%） for PPS. The 95% CI fell within the 10% non-inferiority margin， implying that non-infertility test of the cure rate in the treatment of endpoint disease was valid， and the conclusions of FAS and PPS analysis were consistent. There was no significant difference in the number or course of upper respiratory infection， bronchitis， and pneumonia. The difference in curative effects of TCM syndrome between the two groups after four weeks of treatment was not remarkable. After eight weeks of treatment， the total effective rate of the experimental group was 84.62%（99/117）， statistically higher than 78.15%（93/119） of the control group（χ²=-3.26，P<0.05）. There were no significant differences in the disappearance rates of individual symptoms between the two groups after four weeks of treatment. After eight weeks of treatment， the experimental group and control group exhibited the disappearance rates of 67.50%（54/80） and 47.37%（36/76） for shortness of breath and laziness to speak， 75.00%（54/72） and 53.33%（40/75） for poor appetite， 54.55%（60/110） and 37.84%（42/111） for hyperhidrosis， respectively， with obviously better outcomes observed in the experimental group （P<0.05，P<0.01）. The inter-group comparison revealed significant differences in immune indexes after eight weeks of treatment. As demonstrated by comparison with the situations before treatment， IgA， IgG， IgM， and CD4 did not change significantly after treatment. Except for CD8 in the experimental group (P<0.05), there was no significant difference in other immune indexes before and after treatment There was no significant difference in the incidence of adverse reactions. Conclusion:Longmu Zhuanggu granule is not inferior to pidomod granule in the treatment of children recurrent respiratory infection due to lung-spleen Qi deficiency， and it exhibits good safety， implying its promising clinical application value.

Objective To investigate the correlation between ultrasound-guided diffuse optical tomography (US-DOT) and hypoxia-inducible factor-1Α (HIF-1Α) of breast cancer. Methods Totally 69 patients with pathologically confirmed breast cancer underwent preoperative conventional breast ultrasonography examinations and US-DOT at Peking Union Medical College Hospital From October 2007 to February 2010 were enrolled in this study.After surgery,immunohistochemical staining of HIF-1Α and CD34 were performed,and the differences of total hemoglobin concentration (THC) and microvessel density (MVD) between HIF-1Α positive and negative groups were analyzed. Results HIF-1Α was positive in 12 cases (17.4%) and negative in 57 cases (82.6%). The average THC and MVD of HIF-1Α-positive cases were (274.763±77.661) Μmol/L and (33.8±10.8)/0.2 mm(2) respectively. The average THC and MVD of HIF-1Α-negative cases were (228.059±65.760)Μmol/L and (28.4±7.4)/0.2 mm(2). MVD(t=2.049,P=0.04) and THC(t=2.167,P=0.034) of HIF-1Α-positive group were significantly higher than those of HIF-1Α-negative group. Conclusions HIF-1Α can promote tumor angiogenesis and thus increase the blood supply and THC. As an indicator of tumor blood supply,THC can indirectly reflect the angiogenic activity of breast cancer.
Breast Neoplasms ; diagnostic imaging ; metabolism ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Neovascularization, Pathologic ; Tomography, Optical ; Ultrasonography, Mammary

Objective To analyze the causes of missed diagnosis and misdiagnosis of abdominal organ le -sions through reviewing preoperative transabdominal ultrasound reports .Methods Data of the patients who re-ceived abdominal operation for abdominal organ lesions ( including liver , gallbladder , biliary tract , pancreas , spleen, kidney, adrenal gland, and appendix) in Peking Union Medical College Hospital within the period from March 1 to August 31 in 2013 were exported from pathological workstation .The preoperative ultrasound reports of these patients were reviewed .The missed diagnosis and misdiagnosis cases were recorded , and causes of the mis-takes were analyzed .Results Altogether 58 cases of missed diagnosis or misdiagnosis were identified from 1081 ultrasound reports (5.37%, 58/1081), including 6 liver lesions (5.77%, 6/104, all misdiagnosed), 6 gall-bladder and biliary tract lesions ( 1.30%, 6/462 , 5 missed and 1 misdiagnosed ) , 14 pancreatic lesions (19.72%, 14/71, all missed), 20 kidney and adrenal lesions (6.47%, 20/309, 11 missed and 9 misdiag-nosed), and 12 appendical lesions (16.00%, 12/75, 11 missed and 1 misdiagnosed).The average maximum diameter of the missed nodular lesions was significantly smaller than that of the misdiagnosed lesions ( P =0.001 ) .Conclusions Missed diagnosis and misdiagnosis of ultrasound are attributable to various causes , inclu-ding the nature , location , and size of abdominal organ lesions and the limitation of transabdominal ultrasound technology .The clinical ultrasound examination should be carried out very carefully and thoroughly .Ultrasound radiologists should have a thorough understanding of characteristics of different organ lesions and the limitation of ultrasound technique , in order to avoid missed diagnosis and misdiagnosis in clinical practice .

OBJECTIVETo explore how to determine painful vertebrae treated by kyphoplasty in multiple-level osteoporotic vertebral compression fractures and clinical outcome.

METHODSFrom October 2002 to June 2005, 51 consecutive procedures with kyphoplasty were performed on 35 patients with multiple-level osteoporotic vertebral compression fractures. There were 51 painful vertebrae among 120 vertebral compression fractures. The painful vertebra was determined by the signal intensity changes in MR images, combined with radiography and local percussion pain before operation. Only painful vertebrae were treated by kyphoplasty. Preoperative, postoperative and final follow-up visual analog scale (VAS) and radiographic findings such as vertebral height and Cobb angle were recorded and analyzed.

RESULTSAll patients tolerated the procedure well with immediate relief of their back pain after kyphoplasty and they can walk at 1-3 days after the procedure. There were 3 vertebrae (3/51) occurred asymptomatic extravasation of cement. 31 cases were followed up for mean 16.2 months (range 6-44 months). VAS reduced from preoperative 8.7 to final follow-up 2.1 (P <0. 01). At final follow-up the vertebral height had a recovery rate of 59.17%, and the mean Cobb angle was improved 10.1 degrees. There was a significant improvement between preoperative and final follow-up values (P < 0.01).

CONCLUSIONSThe painful vertebra can be determined by signal intensity changes in MR series images in multiple-level osteoporotic vertebral compression fractures. Selecting painful vertebrae to be treated by kyphoplasty can make patients with multiple-level VCFs gain an excellent result.

Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Fractures, Compression ; diagnosis ; etiology ; surgery ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Osteoporosis ; complications ; Prospective Studies ; Spinal Fractures ; diagnosis ; etiology ; surgery ; Treatment Outcome ; Vertebroplasty ; methods

OBJECTIVETo evaluate the relationship between mortality and HBVDNA and HBeAg expression of severe hepatitis B patients.

METHODSThe mortality rates of different types of severe hepatitis patients in our hospital during the last five years were analysed. HBV DNA was detected using the fluorescence quantitative PCR method and the HBeAg expression of severe hepatitis B was studied using a microparticle method.

RESULTS(1) Hepatitis B morbidity was 83.5% in each type of severe hepatitis, and severe chronic hepatitis B morbidity was 96.77% in each type of severe chronic hepatitis. (2) The mortality rate of those with HBV DNA more than 1 x 10(5) copies/ml was 53.25% and the mortality of those with HBV DNA less than 1 x 10(5) copies/ml was 34.50% (P less than 0.01). The HBeAg expression had no influence on the death rate. (3) The death rate descended to 30.38% from 54.64% (HBV DNA more than 1 x 10(5) copies/ml) when treated with Lamivudine (P less than 0.01).

CONCLUSIONIn severe hepatitis the quantity of virus carried in the patient is one of the key factors of mortality; antivirus treatment can lower mortality.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; DNA, Viral ; Female ; Hepatitis B Surface Antigens ; Hepatitis B virus ; genetics ; immunology ; physiology ; Hepatitis B, Chronic ; diagnosis ; virology ; Humans ; Male ; Middle Aged ; Viral Load ; Young Adult