Cardio-cerebral vascular disease induced by atherosclerosis is a serious cause of human health. The pathogenesis of AS is very complex,and the oxidized low-density lipoprotein( ox LDL) induced foam cells formation is considered to be the most important cytological change in AS. Based on the definition of " TCM chemical biology",we clarified the chemical composition of Ilex hainanensis,the effective substances of I. hainanensis on the activity of anti-AS were screened. Then we found that saponin BF523 had the good inhibitory effect on foam cell formation. In this research,we studied the BF523 as the research object to clarify the molecular target of the active compound of I. hainanensis by foam cell formation model. The results showed that BF523 significantly inhibited the oxidation of ox LDL-induced macrophage foaming and decreased the lipid content in macrophages. BF523 had inhibited the phagocytosis of ox LDL in macrophages by reducing the mRNA and protein levels of scavenger receptor CD36,thereby inhibiting the occurrence and development of AS. These findings not only clarified the mechanism of the inhibition of foam cell formation by saponin BF523,but also provided a useful exploration for the enrichment of the theory of " TCM chemical biology".
Atherosclerosis ; CD36 Antigens ; metabolism ; Cells, Cultured ; Foam Cells ; cytology ; drug effects ; Humans ; Ilex ; chemistry ; Lipoproteins, LDL ; adverse effects

OBJECTIVE: People in Western Africa suffer greatly from febrile jaundice, which is caused by a variety of pathogens. However, yellow fever virus (YFV) is the only pathogen under surveillance in Sierra Leone owing to the undeveloped medical and public health system there. Most of the results of YFV identification are negative. Elucidation of the pathogen spectrum is required to reduce the prevalence of febrile jaundice. METHODS: In the present study, we used Ion Torrent semiconductor sequencing to profile the pathogen spectrum in archived YFV-negative sera from 96 patients in Sierra Leone who presented with unexplained febrile jaundice. RESULTS: The most frequently identified sequencing reads belonged to the following pathogens: cytomegalovirus (89.58%), Epstein-Barr virus (55.21%), hepatitis C virus (34.38%), rhinovirus (28.13%), hepatitis A virus (20.83%), coxsackievirus (10.42%), Ebola virus (8.33%), hepatitis E virus (8.33%), lyssavirus (4.17%), leptospirosis (4.17%), chikungunya virus (2.08%), Crimean-Congo hemorrhagic fever virus (1.04%), and hepatitis B virus (1.04%). CONCLUSION The distribution of sequencing reads suggests a broader spectrum of pathogens for consideration in clinical diagnostics and epidemiological surveillance in Sierra Leone.
Adolescent ; Adult ; Case-Control Studies ; Female ; Fever ; epidemiology ; virology ; Humans ; Jaundice ; epidemiology ; virology ; Male ; Sequence Analysis ; Sierra Leone ; epidemiology ; Young Adult

BACKGROUND: Numerous studies focus on animal models of intervertebral disc degeneration (IDD), but criteria for establishing the animal models of IDD have not been confirmed, and there is a lack of systematic comparison among models. OBJECTIVE: To compare the rat models of IDD established by puncturing at annulus, endplate injection and their combination, thus providing reference for IDD model selection. METHODS: Eighty Sprague-Dawley rats were equivalently randomized into four groups: puncturing group (puncturing at the annulus), endplate injection group (endplate injected with ethyl alcohol), combination group (puncturing at the L5-6annulus and endplate injection at the same segment) and sham operation group. Three rats in each group were taken at postoperative 4, 8, and 12 weeks for X-ray examination to measure the disc height; and the discs were removed for histological observation and immunohistochemical staining. RESULTS AND CONCLUSION: The results of X-ray examination, hematoxylin-eosin staining and immunohistochemical staining all showed that the IDD degree was gradually aggravated in all groups except the sham operation group. At postoperative 4 weeks, compared with the sham operation group, in the endplate injection and combination groups, the percent disc height was significantly decreased, the pathological scores were significantly increased and the average gray value of collagen type I was significantly reduced (P ＜ 0.05). At postoperative 8 and 12 weeks, compared with the sham operation group, the percent disc height in the other three groups were all significantly decreased, the pathological score was significantly increased, and the average gray value of collagen type I was significantly decreased (P ＜ 0.05). Compared with the puncturing and endplate injection group, in the combination group, the percent disc height at postoperative 8 weeks was significantly decreased, and the average gray value of collagen type I at postoperative 12 weeks was significantly decreased (P ＜ 0.05). These results suggest that the rat IDD model can be successfully constructed by above three methods. Puncturing at the annulus is easy to operate and control IDD progression, which can be used to study different stages of IDD. Endplate injection is suitable for the etiological study of IDD, and induces IDD earlier than puncturing, but the final results are similar. The combination method can significantly accelerate IDD aggravation, and thus is not time consuming.

Objective To investigate the safety and efficacy of re-irradiation with stereotactic body radiotherapy(SBRT) for treating locally recurrent advanced pancreatic cancer.Methods From 2014 to 2017,7 patients with stage Ⅲ pancreatic cancer were treated by re-irradiated with SBRT at Shanghai Changhai Hospital.SBRT was delivered via the G4 type cyberknife robotic stereotactic radiosurgery system in all the patients.The median dose of the first SBRT was 35Gy/5-7 fx,and the median dose of re-irradiation with SBRT was 31 Gy/5-8 fx.6 patients had undergone sequential chemotherapy either with gemcitabine or S-1 based therapy except one patient who refused the chemotherapy.Results There were 5 male and 2 female patients.The median overall survival (OS) of 7 patients was 30 months.Patients were re-irradiated with SBRT after a median interval of 10 months after the first SBRT.Median OS and locally relapse-free survival (LFRS) from re-irradiation were 13 months and 11 months,respectively.Three months after re-irradiation,3(42.9％) patients had partial remission and 4 patients had stable disease.Pain disappeared in 4 patients at the end of reirradiation and significant pain was alleviated in 2 patients 1 month after re-irradiation.There were no toxicities of grade 3 or higher grade during two courses of SBRT.Conclusions For patient with locally recurrent advanced pancreatic cancer,SBRT re irradiation regimen was associated with acceptable toxicity,which can effectively alleviate the pain,prolong the survival and improve the life quality.

AIM:To investigate the changes of cardiac structure and function in rats with type 2 diabetic melli-tus(T2DM),and to explore the mechanisms underlying diabetic cardiomyopathy.METHODS:The cardiac structure and function were measured by echocardiography in Zucker diabetic fatty(ZDF)rats and their control Zucker lean(ZL)rats. The size of the cardiomyocytes was determined by wheat germ agglutinin staining.The protein expression of atrial natriuretic peptide(ANP),β-myosin heavy chain(β-MHC), receptor for advanced glycation end products(RAGE), L-type cal-cium channel α1C subunit(CaV1.2)and Orai1 was assessed by Western blot.RESULTS:Compared with the ZL control rats,the thickness of left ventricular wall,ejection fraction(EF),fractional shortening(FS)and the sizes of cardiomyo-cytes were significantly increased,and diastolic function was decreased in the ZDF rats(P<0.05).The protein expression of β-MHC, ANP, RAGE and Orai1 was increased, while the expression of Ca V1.2 was decreased in ZDF rats(P <0.05).CONCLUSION:T2DM rats show the prominent features including cardiomyocyte hypertrophy,ventricular hyper-trophy and compensatory enhancement of cardiac function, and the Ca2+handling and increase in RAGE expression may play important roles in the processes.

Objective To evaluate the efficacy of the ' buddy-in-jail ' technique applied to complex coronary artery lesions during percutaneous coronary intervention.Methods A total of 12640 PCI cases from 4 different hospitals admitted between June 2014 to June 2017 were reviewed. Among them, the balloons or stents were unable to be delivered into the lesions in 25 cases. The "buddy-in-jail"technique was applied in 21 of these 25 cases. According to the guidewires used, the 21 cases were divided into the hydrophilic coated guidewire group(n=9) and non-hydrophilic coated guidewire group(n=21). The rates of procedural success and complications were compared between the 2 groups.Results 18 cases(18/21)were successfully treated with the "buddy-in-jail " technique. The success rates were similar between patients using the same artery(9/11) as the "buddy" vessel patients using other arteries(9/10) (P=0.593). Procedural success rates were also similar between patients using hydrophilic-coated guidewires (7/9) and non- hydrophilic coated guidewires(11/12)(P=0.386). All the wires were successfully taken out without complication.Conclusions "Buddy-in-jail" technique offers a potential alternative approach for patients with difflculty in delivering the balloon or stent to the target lesion.

OBJECTIVETo evaluate the therapeutic efficacy and prognosis of autologous stem Hematopoietic cell transplantation (auto-HSCT) in multiple myeloma (MM) patients.

METHODSA retrospective study was conducted for 56 patients diagnosed with MM and then received auto-HSCT in our hospital from December 2008 to September 2016.

RESULTSAll the patients successfully underwent hematopoietic reconstruction without transplantation-related mortality (TRM). The complete response (CR) rate of all the patients after induction chemotherapy was 23.2% (13/56), while the CR rate of these patients with auto-HSCT increased to 78.6% (44/56) (P<0.01). The CR plus VGPR (very good partial response) rates of these 56 patients after induction chemotherapy and auto-HSCT were 53.6%（30/56）and 94.6%（53/56） respectively (P<0.01). The median progression-free survival (PFS) time and median overall survival (OS) time were 37 and 71 months, respectively. The median PFS time in the patients with induction therapy containing bortezomib was 37 months, however, the median OS time did not reach to 71 months; the median PFS (P<0.01) and the median OS (P<0.01) in the patients with the induction chemotherapy without bortezomib was 27 and 51 months, respectively. Univariate analysis demonstrated that the patients maintained CR or VGPR after auto-HSCT or with less than 6 cycles of induction chemotherapy significantly correlated with PFS (P<0.01).

CONCLUSIONauto-HSCT can further increase the CR rate, prolong PFS and OS time. Sequential auto-HSCT after bortezomib-based therapy is the first line therapy for the transplant-eligible MM patients. Maintenance treatment is beneficial to the sustained CR+VGPR patients after auto-HSCT.

OBJECTIVETo detect the molecular cytogenetic abnormalities of multiple myeloma (MM) by using microrray-based comparative genomic hybridization (array-CGH) technology and to investigate its value of application in MM.

METHODSThe whole-genoine copy number variants (CNV) of bone marrow samples acquired from 20 cases of newly diagnosed MM patients were detected by genome-wide hybridization and scanning by CytoScan 750K Array (Affymetrix). At the same time, the chromosome abnormalities of bone marrow cells were detected by karyotype analysis and FISH using 9 specific probes: D13S319, RB1, p53, 1q21, IgH, IgH/CCND1, IgH/FGFR3, IgH/MAF, IgH/MAFB.

RESULTSAmong the 20 MM patients, the incidence of chromosome abnormalities detected by karyotype analysis, FISH and array-CGH were 15%, 65% and 90%, respectively. The types of CNV detected by array-CGH included the gain (106), loss (156) or UPD (23). There were many different CNVs in every chromosomes except chromosome 5, 9, 18, 21 and Y. Comparison of chromosome abnormalities detected by FISH and array-CGH showed that, the positive ratio of del (13q) was 35% and 40% respectively; the positive ratio of amp (1q) was 40% and 50% respectively; the positive ratio of del (17p) was both 15%. FISH detection showed 8 cases with IgH rearrangement, meansahile the array-CGH detection showed that 4 cases had amp (11q13) (CCND1 gene), 3 cases had amp (16q23) (MAF gene), 1 case had amp (4p16) (FGFR3 gene) and 2 cases had amp (20q12) (MAFB gene). Besides, many other new chromosome abnormalities were found.

CONCLUSIONMore than half of MM patients have cytogenetic changes, and most of them are complex chromosomal abnormalities. By using array-CGH, more chromosome abnormalities can be detected and more cytogenetic information can be provided for clinician.

Pu-erh tea is a unique post-fermented tea processed from tender leaves of Camellia assamica. Characteristic component puerins were produced during the microbial fermentation process.This study focuses on the therapeutic effect and mechanism of puerinⅠ(P1) in Pu-erh tea on ApoE-/- mice with dyslipidemia and diabetes. It was found that P1 could significantly decreased total cholesterol (TC), triglyceride (TG) and fast blood glucose (FBG), and markedly improved impaired glucose tolerance (IPGTT) and insulin sensitivity (ITT) in hyperlipidemic and hyperglycemic ApoE-/- mice. Further experiments proved that P1 reduced FBG and plasma TG levels by inhibiting intestinal α-glycosidase enzymes activity and by activating low-density lipoprotein receptor respectively. This study confirmed the therapeutic effect and mechanism of P1 on ApoE-/- mice with diabetes and hyperlipidemia. Based on the good efficacy of this compound, P1 could be used as a new drug to treat the disorder of glycolipid metabolism.

Focal cerebral ischemia reperfusion is an essential process during ischemic stroke. The apoptosis of vascular endothelial cells induced by ischemia/reperfusion (I/R) injury is an important cause for brain injury after focal cerebral ischemia. Longxuetongluo capsule (LTC) has been used for the treatment of ischemic stroke in clinic. However, its underlying action mechanism is still unclear. This study aimed to verify the protective effect and mechanisms of LTC on HUVEC cells against oxygen-glucose deprivation/reoxygenation (OGD/R) injury through MTT, LDH, flow cytometry, AO/EB staining and western blot assays. As a result, OGD/R significantly decreased the viability of HUVEC cells, which was significantly improved by LTC. LDH release assay showed that OGD/R significantly increased the lactate dehydrogenase (LDH) release, and LTC dramatically reduced the OGD/R-induced LDH release. Further mechanism study indicated that LTC dose-dependently inhibited the cleavage of PARP, caspase 3, and caspase 9 induced by OGD/R, suggesting that LTC could inhibit the activation of caspase 3/9 apoptosis pathway in the OGD/R-induced apoptosis of HUVEC cells. In conclusion, LTC could protect HUVEC cells against OGD/R injury by inhibiting the activation of mitochondria-related caspase 3/9 apoptosis pathway.