Abstract: Malaria, an infectious disease caused by Plasmodium infection, is one of the most important public health problems worldwide. Artemisinin-based combination therapies (ACTs) are recommended by WHO as the first-line treatment for uncomplicated P. falciparum malaria in malaria-endemic areas. The application of artemisinin and its derivatives has played an integral role in reducing the global incidence of malaria. However, in recent years, the emergence and spread of artemisinin resistance has brought great challenges to global malaria control and elimination. At present, the mutation of K13 gene on chromosome 13 of Plasmodium falciparum is most closely related to artemisinin resistance, but in recent years, studies have shown that K13 cannot explain all artemisinin resistance. This article reviews the recent research progress in the field of artemisinin resistance in Plasmodium falciparum, including definition of artemisinin resistance, detection methods and molecular markers related to resistance. In addition, some of the issues discussed in this review remain controversial and require further study.

Objective:To analyze the clinical characteristics of anti-cyclic citrullinated peptide (CCP) antibody-negative rheumatoid arthritis (RA) patients.Methods:To retrospectively analyze the medical records of RA patients hospitalized in the department of rheumatology and immunity of Peking University Third Hospital from January 2013 to December 2018, we collected the baseline characteristics, joint manifestations, extra-articular manifestations, and laboratory parameters of RA patients, and compared the differences between anti-CCP antibody-negative patients and anti-CCP antibody-positive patients by U test and chi-square test. Results:A total of 486 RA patients were included in this study, including 153 anti-CCP antibody-negative patients (31.5%) and 333 anti-CCP antibody-positive patients (68.5%). Compared with anti-CCP antibody-positive group, anti-CCP antibody-negative group had shorter disease course ( U=-4.750, P<0.01) and the pro-portion of morning stiffness, shoulder or elbow joint involvement, and hand arthritis ( P<0.05) was lower, while the incidence of phlebothrombosis of leg ( χ2=4.100, P=0.043) was higher, as well as thrombocytosis ( U=-2.179, P=0.029) and elevation of CRP ( U=-2.154, P=0.03). Subgroup analysis based on RF showed that CCP RF + group had higher percentage of women ( P=0.042) and higher incidence of interstitial lung disease ( χ2=5.652, P=0.017) and secondary Sj?gren's syndrome ( χ2=11.211, P=0.001), compared with CCP RF - group. Conclusion:anti-CCP antibody-negative-patients have similar clinical char-acteristics with anti-CCP antibody-positive group, but the involvement of shoulder or elbow joint and hand arthritis are less common in anti-CCP antibody-negative group. Meanwhile the incidence of phlebothrombosis of leg is higher, and the level of platelet(PLT) and C-reactive protein (CRP) is higher, suggesting that anti-CCP antibody-negative RA may have more vident inflammatory response.

Objective To investigate the diagnosis and treatment of the blunt pancreatic injury.Methods The clinical data of 21 blunt pancreatic trauma patients admitted to our hospital in the past 5 years were analyzed retrospectively.Results 3 of 21 patients were simple blunt pancreatic injury, while the other 18 patients were complicated with other abdominal organs injuries.According to the grading criteria, the number of Ⅰ , Ⅱ, Ⅲ, Ⅳ, Ⅴ grade injury were 4, 7, 5, 3 and 2 cases, respectively, and only 9 patients were diagnosed by CT before operation, and the diagnosis was confirmed during the operation in 11 patients, and 1 was miediagnosed in the first operation.Single drainage or debridement and drainage were performed in 8 cases and distal pancreatectomy with and without spleen were performed in 5 and 3 cases, respectively, and 3patients received pancreaticojejunostomy, 1 received Whipple operation, the other 1 case underwent duodenorrhahy and diverticulation.The mortality rate was 9.5% (2/21), and the complications of pancreatic pseudocyst and fistula developed in 2 (9.5%, 2/21 ) and 5 (23.8%, 5/21 ) cases respectively, and they were cured by drainage, while the other 12 were cured completely.Conclusions The preoperative misdiagnosis rate of pancreatic trauma is high;CT scan should be used to confirm the diagnosis.Careful pancreatic exploration is mandatory and simple and effective surgical procedures with effective drainage is important for treatment success.

Objective To evaluate the therapeutic strategy and effects of surgical treatment for patients with closed trauma of heart valves. Method A total of 32 patients, 28 male and 4 female, aged from 21 to 48 years old with closed trauma of heart valves treated with surgical intervention from June 1987 to November 2008 were retrospectively studied. The duration from trauma to surgical treatment ranged from 18 days to 4 years. Results There was no peri-operative mortality within 30 days. Clinical follow-up for one month to 22 years showed cerebral hemorrhage in only one patient 27 months later and sudden death in one patient probably due to choke of the valve.Conclusions The mortality of patients with closed trauma of heart valves may be decreased by timely and correct diagnosis and treatment, and the outcomes may be improved.

BACKGROUND: Basic fibroblast growth factor (bFGF), a kind of polypeptide growth factor possessing multifunctional biological activities,can protect neurons and promote the growth of nerves. It has been corfirmed that bFGF has therapeutic effects on retina ischemia/reperfusion injury (RIRI).OBJECTIVE: To establish RIRI model and analyze the effects of bFGF on cellular apoptosis of retina and the expression of regulatory gene protein.DESIGN: Randomized grouping and validating trial.SETTING: Department of Ophthalmology, the Affiliated Hospital of Medical College of Qingdao University.MATERIALS: The experiment was conducted at the Research Laboratory of Pathology, Department of Ophthalmology, Medical College of Qingdao University, from April 2002 to December 2003. Twenty-eight healthy Wistar rats were enrolled in this experiment. Four rats were randomly chosen for normal control group, the left eyes of the other 24 rats were set as normal saline control group, and the right eyes were set as bFGF group.METHODS: Normal saline control group and bFGF group adopted the rat RIRI models established by transiently elevating intraocular pressure. Normal saline of 12 μL was injected into the vitreous cavity of the left eyes of the rats in normal control group. 12 μL bFGF was injected into the vitreous cavity of the right eyes of the rats in bFGF group, 4 rats once. No administration was given in normal control group. The expression of apoptotic cells was detected and apoptosis indexes were calculated with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) method and immunohistochemical staining method at the 1st, 6th,12th, 24th,48th and 72nd hours after reperfusion and ischemia for 1 hour.MAIN OUTCOME MEASURES: ① The detection results of apoptotic cells in situ of retina tissuesat different time points after reperfusion. ②The expression of Fas and caspases-2 in retina tissues at different time points after reperfusion.RESULTS ① Comparison of apoptosis indexes of retina tissues at different time points after ischemia reperfusion: There were no apoptotic cells in the retina tissues of the rats in normal control group. As compared with those in normal saline control group, apoptosis indexes in bFGF group were significantly decreased at ischemia 1 hour and reperfusion 1, 6, 12, 24, 48and 72 hours, especially at the 12th, 24th and 48th hours after reperfusion (t =5.362-5.595, P ＜ 0.05). ② The change of Fas expression at different time points after ischemia reperfusion: There was hardly any Fas expression in normal control group. As compared with that in normal saline control group, Fas expression in bFGF group was significantlydecreased at ischemia 1 hour and reperfusion 1, 6, 12, 24, 48 and 72 hours, especially at the 6th, 12th and 24th hours after reperfusion (t=3.954-9.327, P ＜ 0.05). ③The changes of caspase-2 expression at different time points after ischemia reperfusion: There was no caspase-2 expression in normal control group.Compared with that in normal saline control group, the number of caspase2 positive cells in bFGF group was significantly decreased at the 6th,12th,24th, 48th and 72nd hours after ischemia for 1 hour and reperfusion (t=4.125-15.641, P ＜ 0.05).CONCLUSION: bFGF can significantly inhibit the expression of apoptosis gene Fas and caspase-2 in the ischemia and reperfusion of retina, thus reducing cellular apoptosis of ganglion cells and exerting therapeutic effects on the ischemia and reperfusion of retina.

Objective To study the relationship between macular pigment optical density (MPOD) and serum concentration of lutein and zeaxanthin in an adult population.Methods Twenty patients with mild cataract and 39 healthy subjects were enrolled in this study,including 15 males and 44 females.The average age was 43.75 years.Fifty-three subjects were non-smokers and 6 male subjects were smokers.Two subjects preferred meat diet,22 preferred meat-less diet,and 35 have balanced diet.MPOD was measured using heterochromatic flicker photometry at 0.25,0.5,1.0 and 1.75 degrees,and serum concentration of lutein and zeaxanthin was measured using high-performance liquid chromatography.The relationship between MPOD and serum concentration of lutein and zeaxanthin was analyzed.The differences of serum lutein and zeaxanthin between different gender,smokers and non-smokers and subjects with different dietary pattern were also analyzed.Results MPOD at 0.25,0.5,1.0 and 1.75 degrees were 0.59,0.48,0.34 and 0.18,and the average concentration of lutein and zeaxanthin were (0.45± 0.16) μmol/L and (0.11 ± 0.04) μmol/L respectively.Serum concentration of lutein and zeaxanthin in males were slightly higher than that in females,but it was not statistically significant (t=1.13,0.86;P=0.27,0.40).The differences of serum lutien and zeaxanthin between smokers and non-smokers (t=0.15,-0.11;P=0.87,0.91),among subjects of 3 dietary patterns groups were not statistically significant (Flutein=3.87,4.05,0.18;P=0.83,0.81,0.99.Fxeaxanbin=0.99,1.51,0.52;P=0.85,0.68,0.72).There was no correlation between MPOD and serum concentration of lutein (r=-0.06,-0.02,-0.07,0.03;P＞0.05) and zeaxanthin(r=0.02,0.12,0.09,0.11;P＞0.05).Conclusion MPOD was not statistically significantly correlated with serum concentration of lutein and zeaxanthin in the studied population.

Objective:To construct superparamagnetic iron oxide nanoparticles targeting tumor angiogenesis and evaluate their potential value as contrast agent in magnetic resonance imaging (MRI) .Methods:Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles targeting tumor angiogenesis were prepared by using co-precipitation chemical method. Cyclic RGD(cRGD) containing the sequence of Arg-Gly-Asp were conjugated USPIO nanoparticles by using chemical conjugative method to prepare superparamagnetic imaging agent targeting tumor angiogenic vessles. The physical and chemical properties of cRGD-USPIO nanoparticles were detected. The specific binding capabilities of cRGD-USPIO and USPIO to human lung adenocarcinoma cells (A549) and human umbilical vein endothelial cells (HUVEC) were tested by Prussian blue staining. A549 xenografts were established in nude mice, then USPIO and cRGD-USPIO were injected though tail vein, and the MRI signal enhancement effect of cRGD-USPIO was evaluated.Results:We successfully prepared the cRGD-USPIO nanoparticles. Its core diameter was 5-10 nm and the average diameter was (43.97±10.10) nm and the quality saturation magnetic intensity was 59.94 A·m~2·kg~(-1). Cell-binding test suggested that cRGD-USPIO group showed strengthened positive staining. In vivo MRI experiments showed that signals of tumor were significantly reduced in cRGD-USPIO group than that in USPIO group (P<0.01). Conclusion:The constructed cRGD-USPIO nanoparticles can be developed as a potential tumor-specific MRI contrast agent for the early diagnosis of cancer.

Objective To analyze the association of staphylococcal nuclease domain-containing protein 1(SND1) and T-cell intracellular antigen 1(TIA-1) on stress granules, and the regulation of SND1 on stress granules under stress stimuli. Methods The immunofluorescence assay and laser scanning confocal microscopy were used to observe the co-localization of SND1 protein and TIA-1 protein under stress stimuli, and the over-expression plasmids of pEGFP vector were transfected into HeLa cells and to verify which domain of SND1 co-localized with TIA-1 under stress stimuli. RNA interference-mediated knockdown of the expression of SND1 protein in HeLa cells was measured by Western Blotting assay. Then whether the knockdown of SND1 affected the recruitment of TIA-1 on stress granules was observed. Heat shocks under different times were used to identify whether there were dynamic changes in transportation of SND1 and TIA-1 on stress granules. Results SND1 co-localized with TIA-1 on stress granules under stress stimuli, and the associated domain of SND1 were SN domain. TIA-1 still can be recruited on stress granules but a large amount of stress granules were reduced even though the expression of SND1 protein was decreased. And the transportation of SND1 on stress granules was laged behind TIA-1 under different-times of heat shocks. Conclusion SND1 protein co-localizes with TIA-1 on stress granules, and which co-regulates the cellular stress response under stress stimuli.

AIM　To study the structures of the epimerides of cycloclausenamide. METHODS　The structures of compound I, extracted from Clausena lansium (Lour.) Skeels, and synthesized compound III were determined by single crystal X-ray diffraction analysis. The stereo-structures of compound II and IV were also built up through Tripos force field based on crystal structures of compound I and III. RESULTS　The molecular formula and molecular weight were found to be C18H17O2N and 279.34 respectively. Compound I crystallized in monoclinic system, space group P21 with a=0.5928(1), b=1.5014(1), c=1.6190(1) nm, V=1.4410(3) nm3, Z=4, Dx=1.288 g*cm-3, Rf=0.075, Rw=0.073(w=1/σ2｜F｜), S=3.983; compound III crystallized in triclinic system, space group P1 with a=0.5667(1), b=1.2934(1), c=2.1119(1) nm, α=102.17(1), β=90.25(1), γ=102.65(2)°, V=1.4770(5) nm3, Z=4, Dx=1.224 g*cm-3, Rf=0.047, Rw=0.051(w=1/σ2｜F｜), S=0.467. CONCLUSION　These results showed that compound I and III both are cycloclausenamide except that the directions of the phenyl group on C6 are different. Cycloclausenamide can form 4 pairs of epimerides but the directions of the phenyl group does not affect their energy in free state.

Objective To explore the correlation between the efficacy of lamivudine (LAM)therapy and changes of T lymphocyte subsets,CD4+ CD25+ regulatory T lymphocytes (Treg),and levels of interleukin-10 (IL-10)and interferon-gamma (IFN-γ)in the peripheral blood of patients with chronic hepatitis B (CHB).Methods Ninety CHB patients were enrolled in this study.T lymphocyte subsets in the peripheral blood were detected by flow cytometry at baseline and week 52 of LAM therapy.The frequencies of CD4+ CD25+ Treg in the peripheral blood were detected by flow cytometry and levels of IL-10 and IFN-γ were detected by enzyme-linked immunosorbent assay (ELISA)at baseline,week 12,24,36 and 52.The comparisons of overall means between groups and within groups were done by analysis of variance or Dunnett's test.The comparison of means before and after LAM therapy was done by paired t test.Results In 32 complete-responders of 90 CHB patients,the proportions of CD4+ T lymphocytes,CD8+ T lymphocytes and CD4+/CD8+ ratio were increased significantly after LAM therapy (t=4.055、3.267、2.328,all P＜0.05); the frequencies of CD4+CD25+ Treg at baseline,week 12,24,36 and 52 were (5.40±0.60)%,(4.99±0.59)%,(4.54± 0.72)%,(3.86±0.95)% and (3.44±0.76)%,respectively; the levels of IFN-γ,IFN-γ/IL-10 ratio were increased,while the IL-10 level was decreased after LAM therapy.In 43 partial-responders,the proportion of CD4+T lymphocytes and ratio of CD4+/CD8+ were increased after LAM therapy (t= 3.484,2.018,both P＜0.05); the proportion of CD8+ T lymphocytes was not changed significantly after therapy; the frequencies of CD4+ CD25+ Treg at baseline,week 12,24,36 and 52 were (5.65±0.60)%,(5.23±0.63)%,(4.65±0.98)%,(4.42±0.97)% and (4.32±0.82)%,respectively;IFN-γ level,IFN-γ/IL-10 ratio were increased,while IL-10 level was decreased.In 15 non-responders,the proportion of T lymphocyte subsets,the frequency of CD4+ CD25+ Treg,the levels of IFN-γ and IL-10 were not changed significantly after LAM treatment.Conclusions In CHB patients who have achieved response after LAM therapy,the frequency of CD4+ CD25+ Treg in the peripheral blood is decreased,while ratios of CD4+/CD8+ and IFN-γ/IL-10 in the peripheral blood are increased.