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.

Aging can cause degenerative changes in the function of multiple tissues and organs in the body. Gastrointestinal diseases and intestinal dysfunction are very common in the elderly people. The purpose of this study is to explore the effect of the total extract of Astragalus membranaceus (Fisch.) Bge. on intestinal function and gut microbiota homeostasis in natural aging mice, which will provide clues for further mechanism study. The natural aging mice model is established and animal experiments follow the regulations of the Animal Ethics Committee of Nanjing University of Traditional Chinese Medicine. The overall health of the mice was evaluated by the "frailty index" scoring method. The intestinal absorption and transport function were measured by detecting intestinal glucose absorption capacity, transport time, lipase and amylase activities of aging mice. Intestinal inflammation was assessed by detecting inflammatory cytokines by enzyme-linked immunosorbent assay (ELISA). The pathological changes in the intestines of aging mice were tested by hematoxylin-eosin (H&E) staining and alizarin blue (AB) staining. The qRT-PCR method was used to explore the gene transcription level related with the proliferation and differentiation of intestinal stem cells. Microbiota analysis based on 16S rDNA were used to evaluate the composition of gut microbiota. The results showed that Astragalus had a tendency to reduce the "frailty index" of aging mice, but did not show a significant difference. In some indicators of aging phenotype, Astragalus has the most significant effect on hair loss and physical fitness. In terms of intestinal function, Astragalus could increase intestinal glucose absorption capacity, shorten intestinal transportation time and promote lipase secretion in aging mice. The levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-‍α) in the aging intestinal tissue were reduced after Astragalus administration. Astragalus also ameliorated the pathological degeneration of the intestinal tissue of aging mice by increasing the length of small intestinal villi, the thickness of colonic mucosa and goblet cell number. In addition, Astragalus elevated the expression of genes associated with the proliferation and differentiation in jejunum and modulated gut microbiota, especially restoring the abundance of Lachnospiraceae. Taken together, the above research results demonstrate the total extract of Astragalus as a key factor improving the intestinal function and gut microbiota homeostasis of aging mice.

In this study, the ameliorative effects of Flos Abelmoschus manihot on mice with chronic inflammatory bowel disease (IBD) were investigated and its effects on the structure of the intestinal flora as well as the lipid profile in feces of IBD mice were analyzed. All animal welfare and experimental procedures followed the regulations of the Animal Ethics Committee of Nanjing University of Chinese medicine. A mouse model with chronic IBD induced by dextran sulfate sodium (DSS) was used to evaluate changes in body weight, disease activity index (DAI), colonic histopathological damage as well as gene expression levels of inflammatory factors in the colon. Fecal samples from mice in each group were collected and subjected to Illumina high-throughput sequencing to detect the abundance of intestinal flora; samples were analyzed by UHPLC-Q-Exactive^® HF Quadrupole-Orbitrap^® of untargeted lipidomics, which detects lipid content in feces. Administration of Flos Abelmoschus manihot could significantly restore the body weight and ameliorate colonic histopathological damage in IBD mice. Sequencing of the gut microbiota revealed that the species diversity and richness of the gut microbiota in IBD mice were decreased, with a significant increase in the abundance of Verrucomicrobia and a significant decrease in the abundance of Bacteroidetes; Flos Abelmoschus manihot significantly increased the richness and diversity of intestinal microbiota in IBD mice, increased the number of taxa species at each level, and restored the abundance of bacteria in the phylum Bacteroidetes. Analysis of fecal lipid profiles identified the most significant changes in sphingolipid and glycerophospholipid metabolic pathways in IBD mice, with Flos Abelmoschus manihot inhibiting ceramide and sphingomyelin synthesis in sphingolipid metabolism. In summary, Flos Abelmoschus manihot can effectively improve the disease condition of mice with chronic IBD, and it has the effect of regulating intestinal flora homeostasis and lipid metabolism, but the related mechanism between the two still needs to be deeply explored.

OBJECTIVETo compare the predictive values of eight staging systems for primary liver cancer in the prognosis of combined hepatocellular-cholangiocellular carcinoma (cHCC-CC) patients after surgery.

METHODSThe clinical data of 54 cHCC-CC patients who underwent hepatectomy or liver transplantation from May 2005 to Augest 2013 in Chinese PLA General Hospital were collected. We evaluated the prognostic value of the Okuda staging system, Cancer of the Liver Italian Program (CLIP) score, French staging system, Barcelona Clinic Liver Cancer (BCLC) staging system, 7th edition of tumour-node-metastasis (TNM) staging system for hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC), Japan Integrated Staging (JIS) score, and Chinese University Prognostic Index. The distribution, Kaplan-Meier method, Log-rank test, and area under a receiver operating characteristic curve were used to compare the prognosis-predicting ability of these different staging systems in 54 cHCC-CC patients after surgery.

RESULTSThe TNM staging system for ICC and JIS score had a better distribution of cases. The 12-and 24-month survivals of the entire cohort were 65.5% and 56.3%, respectively. A Log-rank test showed that there was a significant difference existing in the cumulative survival rates of different stage patients when using TNM staging system for ICC (stage 1 vs. stage 2, P=0.012; stage 2 vs. stage 3-4, P=0.002), Okuda staging system (stage 1 vs. stage 2, P=0.025), and French staging system (stage A and stage B, P=0.045). The 12-and 24-month area under curve of TNM staging system for ICC, BCLC staging system, JIS score, and CLIP score were 0.836 and 0.847, 0.744 and 0.780, 0.723 and 0.764, and 0.710 and 0.786, respectively.

CONCLUSIONThe 7th edition of TNM staging system for ICC has superior prognostic value to other seven staging systems in cHCC-CC patients undergoing surgical treatment.

Bile Duct Neoplasms ; diagnosis ; surgery ; Carcinoma, Hepatocellular ; diagnosis ; surgery ; Cholangiocarcinoma ; diagnosis ; surgery ; Hepatectomy ; Humans ; Liver Neoplasms ; diagnosis ; surgery ; Neoplasm Staging ; methods ; Predictive Value of Tests ; Prognosis ; ROC Curve ; Survival Rate

Objective To analyze the characteristics of chest CT in children with invasive pulmonary fungal infections(IPFIs),and to explore the influencing factors on chest CT manifestations in children with IPFIs.Methods A retrospective case-control study was conducted to select 97 children with IPFIs from October 2010 to October 2016 in the department of respiratory medicine,PICU and hematology.The children were divided into CT characteristic change group(39 cases) and CT non-characteristic change group(58 cases) according to the chest CT manifestations. Non-conditional multivariate Logistic regression analysis was used to identify the independent influencing factors of CT characteristic changes in children with IPFIs. Results The ratios of less than 3-year-old infants, Candida, the proportion of ICU admission in the CT characteristic change group were lower than those in the CT non-characteristic change group(P<0.05). The proportions of more than 3-year-old, neutropenia,Aspergillus,central venous catheter,hematological malig-nancies were higher than those in the CT non-characteristic change group(P<0.05).Multivariate Logistic regression analysis showed that the hematological malignancies was an independent influencing factor for the characteristic changes of CT in children with IPFIs.Conclusion When children with blood system malignant tumors manifest as fever,cough and other symptoms of infection,chest CT manifestations show characteristic changes,Aspergillus infection should be considered,and empirical antifungal treatment should be focused.

The purpose of this research is to study the effect of small molecule compound piceatannol (PIC) on host inflammation in adenine induced chronic kidney disease (CKD) mice, and then to explore its mechanism based on the regulation of gut microbiota. All procedures were approved by the Institutional Animal Care and Use Committee of the Nanjing University of Chinese Medicine. The level of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was detected by enzyme linked immunosorbent assay (ELISA); UPLC-TQ/MS technology was used to monitor the level of proinflammatory uremic toxin indoxyl sulfate (IS) and p-cresol sulfate (PCS); the expression of occludin was tested by Western blot; in vitro anaerobic culture of gut bacteria was used to produce indole; the abundance of gut microbiota was evaluated by 16S rDNA sequencing. The results showed that PIC had no effect on inflammatory infiltration in kidney tissue of CKD mice, but could decrease IL-6 level in blood and IL-6/TNF-α level in colon tissue. PIC did not improve intestinal occludin protein expression in CKD mice; while it could significantly reduce the levels of IS and PCS in blood and liver of CKD mice. Further mechanism studies showed that PIC could inhibit the synthesis of IS precursor indole in gut bacteria. Moreover, PIC could decrease the abundance of gut bacteria which producing uremic toxin, such as reducing the abundance of indole and p-cresol producing gut bacteria. In conclusion, PIC could regulate gut microbiota and inhibit the synthesis of uremic toxin precursor, thereafter reducing the accumulation of IS and PCS in vivo, ultimately relieving the inflammation of CKD mice.

Objective To evaluate the myocardial systolic function and ventricular remodeling in heart failure rat induced by myocardial infarction (MI) with S/SRI and MMP-9. Methods A total of 70 male SD rats were randomly assigned to 4 groups: 4 weeks and 8 weeks MI ( anterior descending branch of left coronary artery were ligated ) , sham operation (thoracotomy without ligation of coronary artery ) and nonoperated control group. The regional myocardial systolic function of rats was quantified with S/SRI. The myocardial MMP-9 expression was detected by Western blot Results In the 4 weeks MI group, all segment's Ssys, SRsys, the strain of end-systole were reduced while PSI was increased compared to sham and nomoperated group with the exception of the inferior wall. These changes were more significant in 8 weeks MI group compared to the 4 weeks MI group. In the 4 weeks MI group, the expression of MMP-9 was significantly upregulated than the sham operation group and this upregulation was more significant at 8 weeks post MI. Conclusions S/SRI can quantitative evaluate the regional systolic function of heart failure rat induced by myocardial infarction. Progressive upregulation of myocardial MMP-9 expression paralleled the deterioration of regional systolic function in this heart failure rat model.

This study was purposed to establish a real-time fluorescent quantitative PCR (FQ-PCR) for quantifying SALL4 mRNA and to investigate its expression in different types of leukemia patients. SALL4 mRNA expression were measured in 60 leukemia patients of different periods and 10 normal controls sequentially by FQ-PCR. The results showed that the expression of SALL4 mRNA in de novo leukemia patients and relapsed patients was higher than that in controls (P < 0.05), which was significantly decreased at complete remission (CR). In relapsed patients, the expression of SALL4 mRNA increased slightly higher than that in de novo leukemia group, but the difference was not statistically significant (P > 0.05). However, the expression of SALL4 mRNA was low in CLL, T-ALL and AML-M3. The expression pattern of BMI-1 was same as SALL4, and the expression of BMI-1 positively correlated with that of SALL4 in leukemia (r = 0.825, P < 0.01). It is concluded that the detection of SALL4 gene expression in acute and chronic leukemia by real-time gTR-PCR displays high sensitivity and specificity. SALL4 gene may be one of indicators for monitoring the therapeutic outcome of partial leukemia and minimal residual disease.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Leukemia ; genetics ; Male ; Middle Aged ; Neoplasm, Residual ; diagnosis ; RNA, Messenger ; genetics ; Real-Time Polymerase Chain Reaction ; Transcription Factors ; genetics ; Young Adult

OBJECTIVETo explore the effects of adenovirus-delivered tissue inhibitor of metalloprotein- ases-3 (Ad-TIMP-3) on the irradiation sensitivity of human papillomavirus (HPV)-positive cervical cancer cells.

METHODSAn adenovirus expressing TIMP-3 (Ad-TIMP-3), alone or in combination with irradiation,was used to treat HPV-positive cervical cancer cells HeLa-Luc and CaSki. The effects of Ad-TIMP-3 on the proliferation of HeLa-Luc and CaSki cells were detected with MTT assay. The effect of the combination of Ad-TIMP-3 and X-ray on the proliferation of cells were determined by clone formation assay. Twenty nude mice were equally randomly divided into four groups: normal control group,Ad-TIMP-3 group,X-ray group,and combination group. The size of tumor was measured separately,and tumor growth curves were drawn.

RESULTSAd-TIMP-3 significantly inhibited the proliferation of HPV-positive cervical cancer cells in a dose-dependent manner. Combination of Ad-TIMP-3 and X-ray significantly decreased the clones of HeLa-Luc and CaSki than Ad-TIMP-3 or X-ray alone (P<0.05). The tumor weights were (0.216±0.098), (0.276±0.073), and (0.044±0.043) g, respectively, in Ad-TIMP-3 group, X-ray group,and combination group, which were all significantly lower than that in normal control group [(0.534±0.218) g] (all P<0.05). In addition,the tumor weight in the combination group was significantly lower than that in Ad-TIMP-3 group and X-ray group (both P<0.05). The tumor inhibition rate was 59.60%, 48.30%, and 91.80% in X-ray group, Ad-TIMP-3 group and combination group, respectively.

CONCLUSIONSAd-TIMP-3 can effectively inhibit the proliferation of cervical cancer cells. When combined with X-ray,it can remarkably increase the irradiation sensitivity of HPV-positive cervical cancer cells,and thus suppress the tumorigenesis capability of these cells in vivo.

Adenoviridae ; genetics ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Female ; Genetic Vectors ; Humans ; Mice ; Mice, Nude ; Papillomaviridae ; genetics ; Radiation Tolerance ; Tissue Inhibitor of Metalloproteinase-3 ; genetics ; Transfection ; Uterine Cervical Neoplasms ; pathology ; radiotherapy ; virology

OBJECTIVETo investigate the expression of NPM- ALK fusion gene in bone marrow (BM) and peripheral blood (PB) in anaplastic large cell lymphoma (ALCL) patients and its prognostic significance.

METHODSNPM- ALK fusion gene of 21 BM and 15 PB samples from patients with NPM-ALK positive ALCL was detected by RT- PCR, and the relationship between NPM- ALK expression and prognosis and clinical characters was evaluated.

RESULTSOf the 21 patients, 12 cases were male and 9 case were female with a median age of 9 (range, 2-14) years old. The median follow- up was 31 months. Patients with a positive NPM-ALK expression in BM had a 3-years EFS of (35.6±18.6)%, compared with (91.7±8.0)% for patients with negative NPM-ALK (P=0.038). The incidence of positive expression in BM was significantly higher in patients who had more than 3 organs involved by tumor (P=0.032). 86.7% patients had a concordant results of NPM-ALK expression in PB and BM.

CONCLUSIONWe could evaluate the minimal disseminated disease of NPM-ALK positive ALCL patients by screening the NPM-ALK fusion gene in BM and PB by RT-PCR. The positive expression is associated with a poor prognosis and could be used for stratification of ALCL.

Adolescent ; Bone Marrow ; metabolism ; Child ; Child, Preschool ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic ; diagnosis ; genetics ; metabolism ; Male ; Prognosis ; Protein-Tyrosine Kinases ; genetics ; metabolism