MicroRNA-143-3p ameliorates collagen-induced arthritis by polarizing naive CD4+ T cells into Treg cells.

BACKGROUND: Rheumatoid arthritis (RA) is a persistent and systemic autoimmunity disease. The abnormal differentiation of Treg cells is important in pathogenesis. Despite previous studies showed that microRNAs (miRNAs, miR) are pivotal modulators of Treg cells, the effect of miRNAs on Treg cell differentiation and function is not clear. Our study wants to reveal the relationship of miR-143-3p with the differentiative ability and biofunction of Treg cells during the development of RA. METHODS: The Expressing level of miR-143-3p and cell factor generation in peripheral blood (PB) of RA sufferers were identified by ELISA or RT-qPCR. The roles of miR-143-3p in Treg cell differentiation were studied via ShRNA/lentivirus transfection. Male DBA/1 J mice were separated into control, model, control mimics, and miR-143-3p mimics groups to analyze the anti-arthritis efficacy, the differentiative ability of Treg cells, and the expression level of miR-143-3p. RESULTS: Our team discovered that the Expressing level of miR-143-3p was related to RA disease activities in a negative manner, and remarkably related to antiinflammation cell factor IL-10. In vitro, the expression of miR-143-3p in the CD4+ T cells upregulated the percentage of CD4+ CD25+ Fxop3+ cells (Tregs) and forkhead box protein 3 (Foxp3) mRNA expression. Evidently, miR-143-3p mimic intervention considerably upregulated the content of Treg cells in vivo, validly avoided CIA progression, and remarkably suppressed the inflammatory events of joints in mice. CONCLUSION: Our findings indicated that miR-143-3p could ameliorate CIA through polarizing naive CD4+ T cells into Treg cells, which may be a novel strategy to treat autoimmune diseases such as RA.

The role of apoptosis in the pathogenesis of osteoarthritis.

PURPOSE: Apoptosis is an important physiological process, making a great difference to development and tissue homeostasis. Osteoarthritis (OA) is a chronic joint disease characterized by degeneration and destruction of articular cartilage and bone hyperplasia. This purpose of this study is to provide an updated review of the role of apoptosis in the pathogenesis of osteoarthritis. METHODS: A comprehensive review of the literature on osteoarthritis and apoptosis was performed, which mainly focused on the regulatory factors and signaling pathways associated with chondrocyte apoptosis in osteoarthritis and other pathogenic mechanisms involved in chondrocyte apoptosis. RESULTS: Inflammatory mediators such as reactive oxygen species (ROS), nitric oxide (NO), IL-1ß, tumor necrosis factor-α (TNF-α), and Fas are closely related to chondrocyte apoptosis. NF-κB signaling pathway, Wnt signaling pathway, and Notch signaling pathway activate proteins and gene targets that promote or inhibit the progression of osteoarthritis disease, including chondrocyte apoptosis and ECM degradation. Long non-coding RNAs (LncRNAs) and microRNAs (microRNAs) have gradually replaced single and localized research methods and become the main research approaches. In addition, the relationship between cellular senescence, autophagy, and apoptosis was also briefly explained. CONCLUSION: This review offers a better molecular delineation of apoptotic processes that may help in designing new therapeutic options for OA treatment.

Panax notoginseng saponins (PNS) attenuate Th17 cell differentiation in CIA mice via inhibition of nuclear PKM2-mediated STAT3 phosphorylation.

CONTEXT: Rheumatoid arthritis (RA) is an autoimmune disease with aberrant Th17 cell differentiation. Panax notoginseng (Burk.) F. H. Chen (Araliaceae) saponins (PNS) have an anti-inflammatory effect and can suppress Th17 cell differentiation. OBJECTIVE: To investigate mechanisms of PNS on Th17 cell differentiation in RA, and the role of pyruvate kinase M2 (PKM2). MATERIALS AND METHODS: Naive CD4+T cells were treated with IL-6, IL-23 and TGF-ß to induce Th17 cell differentiation. Apart from the Control group, other cells were treated with PNS (5, 10, 20 µg/mL). After the treatment, Th17 cell differentiation, PKM2 expression, and STAT3 phosphorylation were measured via flow cytometry, western blots, or immunofluorescence. PKM2-specific allosteric activator (Tepp-46, 50, 100, 150 µM) and inhibitor (SAICAR, 2, 4, 8 µM) were used to verify the mechanisms. A CIA mouse model was established and divided into control, model, and PNS (100 mg/kg) groups to assess an anti-arthritis effect, Th17 cell differentiation, and PKM2/STAT3 expression. RESULTS: PKM2 expression, dimerization, and nuclear accumulation were upregulated upon Th17 cell differentiation. PNS inhibited the Th17 cells, RORγt expression, IL-17A levels, PKM2 dimerization, and nuclear accumulation and Y705-STAT3 phosphorylation in Th17 cells. Using Tepp-46 (100 µM) and SAICAR (4 µM), we demonstrated that PNS (10 µg/mL) inhibited STAT3 phosphorylation and Th17 cell differentiation by suppressing nuclear PKM2 accumulation. In CIA mice, PNS attenuated CIA symptoms, reduced the number of splenic Th17 cells and nuclear PKM2/STAT3 signaling. DISCUSSION AND CONCLUSIONS: PNS inhibited Th17 cell differentiation through the inhibition of nuclear PKM2-mediated STAT3 phosphorylation. PNS may be useful for treating RA.

Plant begomoviruses subvert ubiquitination to suppress plant defenses against insect vectors.

Most plant viruses are vectored by insects and the interactions of virus-plant-vector have important ecological and evolutionary implications. Insect vectors often perform better on virus-infected plants. This indirect mutualism between plant viruses and insect vectors promotes the spread of virus and has significant agronomical effects. However, few studies have investigated how plant viruses manipulate plant defenses and promote vector performance. Begomoviruses are a prominent group of plant viruses in tropical and sub-tropical agro-ecosystems and are transmitted by whiteflies. Working with the whitefly Bemisia tabaci, begomoviruses and tobacco, we revealed that C2 protein of begomoviruses lacking DNA satellites was responsible for the suppression of plant defenses against whitefly vectors. We found that infection of plants by tomato yellow leaf curl virus (TYLCV), one of the most devastating begomoviruses worldwide, promoted the survival and reproduction of whitefly vectors. TYLCV C2 protein suppressed plant defenses by interacting with plant ubiquitin. This interaction compromised the degradation of JAZ1 protein, thus inhibiting jasmonic acid defense and the expression of MYC2-regulated terpene synthase genes. We further demonstrated that function of C2 protein among begomoviruses not associated with satellites is well conserved and ubiquitination is an evolutionarily conserved target of begomoviruses for the suppression of plant resistance to whitefly vectors. Taken together, these results demonstrate that ubiquitination inhibition by begomovirus C2 protein might be a general mechanism in begomovirus, whitefly and plant interactions.

MicroRNA-26b-5p alleviates murine collagen-induced arthritis by modulating Th17 cell plasticity.

Rheumatoid arthritis (RA) is a chronic autoimmune disease, and the abnormal differentiation of IL-17-producing T helper (Th17) cells is an important factor in the pathogenesis. Previous studies have shown that microRNAs (miRNAs, miR) act as key regulators of Th17 cells. However, the effects of miRNAs on Th17 cell differentiation and plasticity in RA are not clear. In this study, not only low miR-26b-5p expression and high IL-17A level were observed in the peripheral blood of RA patients, but also the negative correlation between miR-26b-5p and IL-17A was explored. The changes in collagen-induced arthritis (CIA) mice were consistent with those in RA patients. The results of in vitro experiments showed that miR-26b-5p mainly inhibited the initial differentiation of Th17 cells but did not impact the differentiation of induced-Treg into Th17-like cells. Meanwhile, miR-26b-5p mimics treatment alleviated inflammatory responses and reduced Th17 proportion in CIA mice. These results indicated that miR-26b-5p could alleviate the development of mice CIA by inhibiting the excessive Th17 cells, and that miR-26b-5p could modulate the plasticity of Th17 cell differentiation in RA, mainly block the initial differentiation. This may provide a novel strategy for the clinical treatment of RA.

Supporting her as the situation changes: A qualitative study of spousal support strategies for patients with breast cancer in China.

OBJECTIVE: Spouses who are the major source of social support for married breast cancer patients sometimes do not know how to support the patient effectively. This study aimed to investigate the experiences and strategies of spouses identified as supportive for patients throughout the disease. METHODS: A qualitative study using semi-structured in-depth interviews was conducted with 22 husbands of Chinese women with breast cancer, who had effectively supported their wives. Thematic analysis was used for data analysis. RESULTS: Three themes emerged from the data: (a) following the diagnosis, the spouse focused on "problem solving under stress" by preparing the patient for the physician's disclosure of the diagnosis, helping her to cope with the shock, and aiding her in dealing with the treatment recommendations; (b) during treatment, the spouse focused on "functional compensation" to offset the patient's reduced self-care and family care abilities; and (c) following treatment, the spouse focused on "role return" by adapting to changes in the patient and assisting her return to the family and society. CONCLUSION: Chinese spouses of women with breast cancer exhibited support strategies that varied with disease progress. Healthcare providers should aid spouses in providing support according to the changing needs of patients with breast cancer.

Vector development and vitellogenin determine the transovarial transmission of begomoviruses.

The majority of plant viruses are transmitted by insect vectors between hosts, and transovarial transmission of viruses from vector parents to offspring has great significance to their epidemiology. Begomoviruses are transmitted by the whitefly Bemisia tabaci in a circulative manner and are maintained through a plant-insect-plant cycle. Other routes of begomovirus transmission are not clearly known. Here, we report that transovarial transmission from female whiteflies to offspring often happens for one begomovirus, Tomato yellow leaf curl virus (TYLCV), and may have contributed significantly to its global spread. We found that TYLCV entry of the reproductive organ of its vector mainly depended on the developmental stage of the whitefly ovary, and the transovarial transmission of TYLCV to offspring increased with whitefly adult age. The specific interaction between virus coat protein (CP) and whitefly vitellogenin (Vg) was vital for virus entry into whitefly ovary. When knocking down the expression of Vg, the entry of TYLCV into ovary was inhibited and the transovarial transmission efficiency decreased. In contrast, another begomovirus, Papaya leaf curl China virus (PaLCuCNV), CP did not interact with whitefly Vg, and PaLCuCNV could not be transovarially transmitted by whiteflies. We further showed that TYLCV could be maintained for at least two generations in the absence of virus-infected plants, and the adult progenies were able to infect healthy plants in both the laboratory and field. This study reports the transovarial transmission mechanism of begomoviruses, and it may help to explain the evolution and global spread of some begomoviruses.

Vector and nonvector insect feeding reduces subsequent plant susceptibility to virus transmission.

The interactions of vector-virus-plant have important ecological and evolutionary implications. While the tripartite interactions have received some attention, little is known about whether vector infestation affects subsequent viral transmission and infection. Working with the whitefly Bemisia tabaci, begomovirus and tobacco/tomato, we demonstrate that pre-infestation of plants by the whitefly vector reduced subsequent plant susceptibility to viral transmission. Pre-infestation by the cotton bollworm, a nonvector of the virus, likewise repressed subsequent viral transmission. The two types of insects, with piercing and chewing mouthparts, respectively, activated different plant signaling pathways in the interactions. Whitefly pre-infestation activated the salicylic acid (SA) signaling pathway, leading to deposition of callose that inhibited begomovirus replication/movement. Although cotton bollworm infestation elicited the jasmonic acid (JA) defense pathway and was beneficial to virus replication, the pre-infested plants repelled whiteflies from feeding and so decreased virus transmission. Experiments using a pharmaceutical approach with plant hormones or a genetic approach using hormone transgenic or mutant plants further showed that SA played a negative but JA played a positive role in begomovirus infection. These novel findings indicate that both vector and nonvector insect feeding of a plant may have substantial negative consequences for ensuing viral transmission and infection.

Genetic variation and population structure of Cucumber green mottle mosaic virus.

Cucumber green mottle mosaic virus (CGMMV) is a single-stranded, positive sense RNA virus infecting cucurbitaceous plants. In recent years, CGMMV has become an important pathogen of cucurbitaceous crops including watermelon, pumpkin, cucumber and bottle gourd in China, causing serious losses to their production. In this study, we surveyed CGMMV infection in various cucurbitaceous crops grown in Zhejiang Province and in several seed lots purchased from local stores with the dot enzyme-linked immunosorbent assay (dot-ELISA), using a CGMMV specific monoclonal antibody. Seven CGMMV isolates obtained from watermelon, grafted watermelon or oriental melon samples were cloned and sequenced. Identity analysis showed that the nucleotide identities of the seven complete genome sequences ranged from 99.2 to 100%. Phylogenetic analysis of seven CGMMV isolates as well as 24 other CGMMV isolates from the GenBank database showed that all CGMMV isolates could be grouped into two distinct monophyletic clades according to geographic distribution, i.e. Asian isolates for subtype I and European isolates for subtype II, indicating that population diversification of CGMMV isolates may be affected by geographical distribution. Site variation rate analysis of CGMMV found that the overall variation rate was below 8% and mainly ranged from 2 to 5%, indicating that the CGMMV genomic sequence was conservative. Base substitution type analysis of CGMMV showed a mutational bias, with more transitions (A↔G and C↔T) than transversions (A↔C, A↔T, G↔C and G↔T). Most of the variation occurring in the CGMMV genome resulted in non-synonymous substitutions, and the variation rate of some sites was higher than 30% because of this mutational bias. Selection constraint analysis of CGMMV ORFs showed strong negative selection acting on the replication-associated protein, similar to what occurs for other plant RNA viruses. Finally, potential recombination analysis identified isolate Ec as a recombinant with a low degree of confidence.

A host plant genome (Zizania latifolia) after a century-long endophyte infection.

Despite the importance of host-microbe interactions in natural ecosystems, agriculture and medicine, the impact of long-term (especially decades or longer) microbial colonization on the dynamics of host genomes is not well understood. The vegetable crop 'Jiaobai' with enlarged edible stems was domesticated from wild Zizania latifolia (Oryzeae) approximately 2000 years ago as a result of persistent infection by a fungal endophyte, Ustilago esculenta. Asexual propagation via infected rhizomes is the only means of Jiaobai production, and the Z. latifolia-endophyte complex has been maintained continuously for two centuries. Here, genomic analysis revealed that cultivated Z. latifolia has a significantly smaller repertoire of immune receptors compared with wild Z. latifolia. There are widespread gene losses/mutations and expression changes in the plant-pathogen interaction pathway in Jiaobai. These results show that continuous long-standing endophyte association can have a major effect on the evolution of the structural and transcriptomic components of the host genome.

[Effect of Qingluo Tongbi Compound on Osteoclast Differentiation-related mIRNA Expressions in Adjuvant Induced Arthritis Rats].

Objective To observe the effect of Qingluo Tongbi Compound (QTC) on osteoclast dif- ferentiation-related miRNA expressions in adjuvant induced arthritis (AIA) rats, and to study its mecha- nism for treating rheumatoid arthritis (RA). Methods The synovial fibroblasts and monocytes of peripher- al blood from AIA rats were co-cultured to induce osteoclast-like cells. Differently expressed miRNAs in the late stage osteoclasts differentiation were detected by miRCURY™ Array. Real-time quantitative PCR (RT- PCR) was applied to verify the reliability of miRNA array. QTC drug-containing sera and blank sera were prepared and added to the co-cultured system. The osteoclasts were randomly divided into three groups, the blank group, the blank serum group, and the QTC group. RT-PCR was applied to detect the effect of QTC on related differentially expressed miRNAs. Bioinformatics software was applied to analyze related differentially expressed miRNAs. Results miRNA array results showed that as compared with the monocytes group, there were 211 miRNAs differentially expressed in osteoclast-like cell differentiation, including 88 up-regulated miRNAs and 123 down-regulated miRNAs. Results of RT-PCR were consistent with results of the array. RT-PCR showed that the expression level of miR-140-5p was obviously up-regulated after the intervention of QTC. Results of bioinformatics analyses showed that the target gene of miR-140-5p was sig- nificantly enriched in signaling pathways such as the regulation of actin cytoskeleton, Ras signaling path- ways, cAMP signaling pathways, and Rap1 signaling pathways. Conclusions There were various dysregulated expressions of miRNAs in the anaphase of osteoclast-like cells differentiation. QTC participated the regulation of osteoclast differentiation by effecting the expression of miR-140-5p.

[The Real World Study on Evaluating the Effect of Chinese Medicine Combined Western Medicine in Treating Rheumatoid Arthritis].

Objective To observe the curative effect of Chinese medicine (CM) combined West- ern medicine (WM) in treating rheumatoid arthritis (RA) patients. Methods Totally 351 RA patients were allocated into two groups by their willingness, 52 cases in the control group and 299 cases in the combination group. Treatment of WM mainly included non-steroidal anti-inflammatory drugs, glucocorti- coids, and anti-rheumatic drugs. And treatment based on syndrome differentiation of CM was adopted. Four diagnostic information of CM, joint pain, tenderness, swelling index, laboratory indices, and treat- ment expenses were observed. Disease activity score 28 (DAS28) , quality of life score [health assessment questionnaire (HAQ) ] , and efficacy of disease were assessed. Results After 2-3 months of treatment, the total effective rate was higher in the combination group than in the control group (P < 0. 05). After 6-12 months of treatment, the total effective rate, DAS28, and HAQ score were better in the combination group than in the control group (P <0. 05). There was no statistical difference in use of Western drugs, total expenses of hospitalization, total expenses of outpatient service between the two groups (P >0. 05). Patients who were treated by combined treatment, or having higher DAS obtained better effects after 2-3 months of treatment (P <0. 05). Patients who were treated by combined treatment, or having lower DAS obtained better effects after 6-12 months of treatment (P <0. 05). Conclusions Real world study (RWS) observed that combined CM and WM could get more significant effect. It also could effectively reduce disease activity, improve patients' QOL, with no economic burdens added.

[Metabolomics analysis of Tripterygium wilfordii formulation based on theory of detoxicity compatibility].

Tripterygium wilfordii Hook. f. induced-hepatotoxicity was the main limitation for its usage in clinic. Qingluo Tongbi formulation showed obvious attenuation for hepatotoxicity in clinic and fundamental research in vivo. To explore the potential mechanism of the attenuation, we conducted a study on the plasma metabolomic profiles of T. wilfordii and Qingluo Tongbi formulation in rats by a sensitive gas chromatography-mass spectrometry (GC-MS/MS) method. In plasma samples, a total of 72 compounds were analyzed by EI source MS, and were successfully identified by matching NIST database. The semi-quantification results were then calculated by OPLS-DA model with SIMCA-P 13.0 software. The three groups were clearly distinguished in OPLS-DA score plot. In addition, the observation values of Qingluo Tongbi formulation showed the obvious trend towards the control levels, suggesting the detoxicity effect of the formulation. Variation metabolites were further analyzed by VIP and One Way ANOVAs, and the results showed a significant increase in compounds of glycogenic amino acids, such as alanine, proline, serine and glutamine after the administration of T. wilfordii, indicated that the tissue proteins were decomposed and amino acids were leakage into blood. Qingluo Tongbi formulation could reverse the amino acids into normal level. On the contrary, the levels of glucose, lactic acid and hydroxy butyrate decrease, and the formulation can relieve the disorder in the levels of lactic acid, suggesting the regulation of the energy metabolism. Additionally, the level of branched chain amino acid was decreased, suggested the toxicity was induced, but the formulation cannot increase it into the normal levels. Nevertheless, all the above results suggested that the classical Qingluo Tongbi formulation displayed the liver protection effect by adjusting the amino acid levels and regulating the energy metabolism. Qingluo Tongbi formulation was developed based on traditional Chinese medicine theory "detoxicity compatibility", and contained Panax notoginseng (Burk.) F. H. Chen to nourish blood and absorb clots. Modern pharmacology suggested that its liver protection effect was correlated with the promotion of protein synthesis. Another important herb is Rehmannia glutinosa Libosch., which can regulate the energy metabolism. Both were consistent with the metabolomic results in this study, which explained the potential mechanism of "detoxicity compatibility" theory. Therefore, the currently developed metabolomic approach and the obtained results would be highly useful for the comprehensive toxicity studies for other herbal medicines and various complex deoxicity formulations.

Specific cells in the primary salivary glands of the whitefly Bemisia tabaci control retention and transmission of begomoviruses.

UNLABELLED: The majority of plant viruses are vectored by arthropods via persistent-circulative or noncirculative transmission. Previous studies have shown that specific binding sites for noncirculative viruses reside within the stylet or foregut of insect vectors, whereas the transmission mechanisms of circulative viruses remain ambiguous. Here we report the critical roles of whitefly primary salivary glands (PSGs) in the circulative transmission of two begomoviruses. The Middle East Asia Minor 1 (MEAM1) species of the whitefly Bemisia tabaci complex efficiently transmits both Tomato yellow leaf curl China virus (TYLCCNV) and Tomato yellow leaf curl virus (TYLCV), whereas the Mediterranean (MED) species transmits TYLCV but not TYLCCNV. PCR and fluorescence in situ hybridization experiments showed that TYLCCNV efficiently penetrates the PSGs of MEAM1 but not MED whiteflies. When a fragment of the coat protein of TYLCCNV was exchanged with that of TYLCV, mutated TYLCCNV accumulated in the PSGs of MED whiteflies, while mutant TYLCV was nearly undetectable. Confocal microscopy revealed that virion transport in PSGs follows specific paths to reach secretory cells in the central region, and the accumulation of virions in the secretory region of PSGs was correlated with successful virus transmission. Our findings demonstrate that whitefly PSGs, in particular the cells around the secretory region, control the specificity of begomovirus transmission. IMPORTANCE: Over 75% of plant viruses are transmitted by insects. However, the mechanisms of virus transmission by insect vectors remain largely unknown. Begomoviruses and whiteflies are a complex of viruses and vectors which threaten many crops worldwide. We investigated the transmission of two begomoviruses by two whitefly species. We show that specific cells of the whitefly primary salivary glands control viral transmission specificity and that virion transport in the glands follows specific paths to reach secretory cells in the central region and then to reach the salivary duct. Our results indicate that the secretory cells in the central region of primary salivary glands determine the recognition and transmission of begomoviruses. These findings set a foundation for future research not only on circulative plant virus transmission but also on other human and animal viruses transmitted by arthropod vectors.

Higher proliferation of peritumoral endothelial cells to IL-6/sIL-6R than tumoral endothelial cells in hepatocellular carcinoma.

BACKGROUND: This study aimed to explore the responses to the interleukin-6 (IL-6)/soluble interleukin-6 receptor (sIL-6R) complex in peritumoral endothelial cells (PECs) and tumor endothelial cells (TECs), as well as determine the signaling pathways in the angiogenesis of hepatocellular carcinoma (HCC). METHODS: The expression of IL-6, IL-6R, gp130, CD68, HIF-1α, and microvessel density (MVD) were assessed with an orthotopic xenograft model in nude mice. ECs were incubated under hypoxic conditions to detect IL-6 and gp130. The proliferation of PECs and TECs in the presence of IL-6 and sIL-6R, as well as the expression of gp130, JAK2/STAT3, PI3K/AKT in endothelial cells were measured. RESULTS: Peritumoral IL-6, IL-6R, gp130, CD68, and HIF-1α expression, as well as MVD, gradually increased during tumor growth. Hypoxia could directly induce IL-6 expression, but not gp130 in PECs. The co-culture of IL-6/sIL-6R induced much higher PEC proliferation and gp130 expression, as well as the elevated phosphorylation of JAK2 and STAT3, however not the phosphorylation of PI3K and AKT. CONCLUSIONS: PECs exhibited higher proliferation in response to IL-6/sIL-6R co-treatment compared with TECs in HCC via the up-regulation of gp130 /JAK2/STAT3. PEC and its associated peritumoral angiogenesis microenvironment may be a potential novel target for anti-angiogenic treatment.

[comparisons of pharmacokinetic profile of eleven bioactive components in Haizao Yuhu decoction modified with Haizao and Gancao anti-drug pair in normal rats].

Haizao Yuhu decoction (HYD) is a formula that has been used for approximately 500 years and famous for its efficiency in treating thyroid-related diseases in traditional Chinese medicine (TCM). HYD was first presented by Chen Shi-gong in a famous surgical monograph named Waike Zhengzong during the Ming Dynasty. We conducted the research to investigate the possible pharmacokinetic profile of different prescriptions of HYD in rats, in order to reveal the interactions of Haizao and Gancao drug pair with other herbs in HYD. Liquiritin, naringin, besperidin, peimine, peiminine liquiritigenin, glycyrrhizic acid, hergapten, nobiletin, osthole, glycyrrhetinic acid in blood samples were determined by UPLC-MS/MS. The result revealed tbat Haizao could enhance the peak concentration of glycyrrhizic acid. The other herbs in HYD may promote'the absorption of flavonoids in Gancao in normal rats, but inhibit the absorption of saponins and accelerate their metabolism. Gancao and Haizao drug pair could enhance the bioavailability of hesperidin, peimine, bergapten, nobiletin and osthole and prolong the elimination of peimine and naringin.

Optimal treatment opportunity for mTHPC-mediated photodynamic therapy of liver cancer.

Photodynamic therapy (PDT) has been clinically used for liver cancer. The pharmacokinetics of a photosensitizer needs to be monitored so that PDT can be performed at the most favorable time and with the proper dose to increase the cure rate. As mTHPC is a fluorescent compound, we investigate its pharmacokinetics, distribution, and elimination in the rat orthotropic liver cancer model in order to confirm an optimal treatment opportunity of liver cancer PDT. After intravenous administration at a single dose of 300 µg/kg, mTHPC was extracted from tissue homogenates or plasma. Then, mTHPC concentrations were assessed by fluorescence spectroscopy and the data were processed with PK-GRAPH pharmacokinetic procedure. The plasma concentration-time profile of mTHPC showed a short distribution half-life (T½α = 0.082 h) and a relatively longer elimination half-life (T½ß = 28.23 h), which quite fitted with a two-compartment model. The results of mTHPC tissue distributions showed that the highest drug accumulation was in tumor tissue, and successively decreased in liver, heart, spleen, muscle, and skin tissues. The drug distribution ratio of tumor to normal tissue reached the peak at 24 h after mTHPC administration. mTHPC was eliminated at a suitable rate in rat orthotropic liver cancer model, and there was no long-term accumulation of mTHPC in rat tissues. For PDT of orthotropic liver cancer, 24 h after mTHPC intravenous injection may be the optimal treatment time point, which might provide higher clinical efficacy and reduce side effects.

[Experiences of Professor Zhou Zhong-ying in diagnosing and treating rheumatoid arthritis by data mining].

OBJECTIVE: To summarize Professor ZHOU Zhong-ying's academic ideas and clinical experiences in diagnosing and treating rheumatoid arthritis (RA). METHODS: Totally 153 clinical case reports were recruited. Data mining techniques like frequencies, factor analysis, and association analysis were used in order to find out laws of syndrome, pathogenesis, treatment methods, formulae and medication. RESULTS: By statistical analyses, we found 14 main symptoms, 76 commonly used clinical drugs, 8 core prescriptions for RA, and the correlation between main pathogeneses and related drugs. CONCLUSION: Results analyzed and summarized from mining his experiences in RA treatment were in line with clinical practice.

[The effect of drainage in cavities on preventing from grade B and C of the pancreatic fistula after pancreaticoduodenectomy].

OBJECTIVE: To explore the effect of drainage in cavities on preventing from grade B and C of the pancreatic fistula after pancreaticoduodenectomy (PD). METHODS: From June 2008 to June 2010, the medical team had performed the operations of digestive tract reconstruction by the same way in 68 cases with PD. There were 43 male and 25 female patients, with a mean age of (64 ± 3) years. The patients were simply randomly divided into drainage in cavities group (DC, n = 32) and conventional drainage group (CD, n = 36) according to the different drainage way. The methods of drainage in cavities were composed of three aspects which include drainage in main pancreatic duct, drainage around cholecystojejunostomy anastomosis and peripancreatic drainage. The clinical parameters of the two groups were collected. The characteristics of the drainage juice which include color, volume and amylase value in the two groups were compared. The incidence and severity grading of pancreatic fistula between the two groups were evaluated. RESULTS: The average of amylase value and the peripancreatic drainage flow were (1401 ± 8) U/L and (49 ± 5) ml in the DC group. Their average in the CD group were (2160 ± 13) U/L and (76 ± 4) ml. There was significant statistical difference in the peripancreatic drainage flow between the two groups (t = 2.597, P = 0.031). The amylase values of the drainage juice between the two groups were of no statistical difference (P > 0.05). According to the definition of pancreatic fistula by an international study group, the incidence of pancreatic fistula in the DC group was 25.0% (8/32) and the CD group 30.5% (11/36) (P > 0.05). The proportion of grades B and C of pancreatic fistula in the DC group had statistical difference compared with one of the CD group (χ(2) = 4.797, P = 0.029). CONCLUSION: Drainage in cavities could significantly decrease and the occurring ratio of grade B and C of pancreatic fistula after PD.

[Comprehensive measures for improving the radical resection rate and safety of Bismuth-Corlette type III hilar cholangiocarcinoma].

OBJECTIVE: To investigate the comprehensive measures for improving radical resection rate and safety of Bismuth-Corlette type III hilar cholangiocarcinoma. METHODS: The clinical data of 15 patients with Bismuth-Corlette type III hilar cholangiocarcinoma who performed radical resection from June 2009 to December 2011 was analyzed retrospectively. There were 11 male and 4 female patients, aged from 45 to 74 years (mean 59 years). The preoperative evaluation were conducted by using magnetic resonance cholangiopancreatography (MRCP), dual source spiral CT combined with IQQA-Liver CT Imaging Analysis System providing three-dimensional reconstruction of tumor, bile duct, hepatic artery and portal vein, which could help to chose the appropriate treatment modality. All patients were treated with selective hemi-hepatic vascular control of removal liver, hemi-hepatectomy combined with whole caudate lobe resection and regional lymphadenectomy. The merits of each evaluation methods and measures of surgical treatment were analyzed thoroughly. RESULTS: The preoperative evaluation modalities including the dual source spiral CT combined with IQQA-Liver CT Imaging Analysis System could clearly show the involvement of bile duct, hepatic artery and portal vein invaded by the tumor. The satisfactory postoperative recovery could be achieved by the remnant liver volume of > 40% after the hemi-hepatectomy combined with whole caudate lobe resection through the selective preoperative biliary drainage and hemihepatic vascular control. The mean complication was transient aggravated liver dysfunction. There was no death reported during perioperative period in the group. CONCLUSIONS: The preoperative imaging evaluation modalities including MRCP, dual source spiral CT combined with IQQA-Liver CT Imaging Analysis System could do favor for the preoperative evaluation of invasion degree of hilar cholangiocarcinoma and the selection of appropriate surgical treatment. Hemi-hepatectomy combined with whole caudate lobe resection and regional lymphadenectomy could be an alternative management of Bismuth-Corlette type III hilar cholangiocarcinoma.