Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Purpose: The European Organization for Research and Treatment of Cancer quality of life (QOL) questionnaires (QLQ-C30, QLQ-OG25, and QLQ-STO22) are widely used for the assessment of gastric cancer patients. This study aimed to use these questionnaires to evaluate QOL in postgastrectomy patients. Methods: We prospectively evaluated 106 patients with distal gastrectomy (DG), 57 with pylorus-preserving gastrectomy (PPG), and 117 with total gastrectomy (TG). Body weight and QOL questionnaires were evaluated preoperatively and postoperatively (at 3 weeks, and 3, 6, and 12 months). Results: TG patients had significantly more weight loss than DG/PPG patients. Compared with DG, patients after PPG had less dyspnea (P = 0.008) and trouble with coughing (P = 0.049), but more severe symptoms of insomnia (P = 0.037) and reflux (P = 0.030) at postoperative 12 months. Compared with DG/PPG, TG was associated with worse body image, dysphagia, eating, and taste in both OG25 and STO22. Moreover, OG25 revealed worse QOL in the TG group with respect to odynophagia, eating with others, choked when swallowing, trouble talking, and weight loss. The QOL of patients who received chemotherapy was worse than those in the chemo-free group in both physical functioning and symptoms such as nausea/vomiting, appetite loss, and trouble with taste; however, these side effects would soon disappear after finishing chemotherapy. Conclusion PPG was similar to DG in terms of postoperative QOL and maintaining body weight, while TG was always inferior to both DG and PPG. Adjuvant chemotherapy can affect both body weight and QOL despite being reversible.

ObjectiveTo investigate the drug-resistant gene polymorphisms in Plasmodium falciparum imported from Equatorial Guinea to Shandong Province. MethodsFrom 2015 to 2016, blood samples were collected from imported P. falciparum malaria patients returning from Equatorial Guinea to Shandong Province, and genome DNA of the malaria parasite was extracted. The drug-resistant Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and K13 genes of P. falciparum were amplified using a PCR assay, followed by DNA sequencing, and the sequences were aligned. Results The target fragments of all 5 drug-resistant genes of P. falciparum were successfully amplified and sequenced. There were 72.8%, 18.6%, and 8.6% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfcrt gene, respectively, and all mutant haplotypes were CVIET (the underline indicates the mutation site). There were 20.0%, 61.4% and 18.6% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfmdr1 gene, respectively, and the mutant haplotypes mainly included YF and NF (the underlines indicate the mutation sites). There were 1.4%, 98.6%, and 0 of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfdhfr gene, respectively, and AIRNI was the predominant mutant haplotype (the underline indicates the mutation site). There were 1.4%, 94.3%, and 4.3% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfdhps gene, respectively, and SGKAA was the predominant mutant haplotype (the underline indicates the mutation site). The complete drug-resistant IRNGE genotype consisted of 8.6% of the Pfdhfr and Pfdhps genes, and the K13 gene A578S mutation occurred in 1.4% of the parasite samples. Conclusions There are mutations in the Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and K13 genes of P. falciparum imported from Equatorial Guinea to Shandong Province, with a low frequency in the Pfcrt gene mutation and a high frequency in the Pfmdr1, Pfdhfr, and Pfdhps gene mutations, and the K13 gene A578S mutation is detected in the parasite samples.

Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as macrophage polarization, of which play an important role in the pathogenesis of many diseases. Numerous studies have proved that Hesperidin (HDN), a traditional Chinese medicine, extracted from fruit peels of the genus citrus, play key roles in anti-inflammation, anti-tumor, anti-oxidant and so on. However, the role of HDN in macrophage polarization has never been reported. Additional, because of its poor water solubility and bioavailability. Our laboratory had synthesized many hesperidin derivatives. Among them, hesperidin derivatives-12 (HDND-12) has better water solubility and bioavailability. So, we evaluated the role of HDND-12 in macrophage polarization in the present study. The results showed that the expression of Arginase-1 (Arg-1), interleukin-10 (IL-10), transforming growth factor β (TGF-β) were up-regulated by HDND-12, whereas the expression of inducible Nitric Oxide Synthase (iNOS) was down-regulated in LPS- and IFN-γ-treated (M1) RAW264.7 cells. Moreover, the expression of p-JAK2 and p-STAT3 were significantly decreased after stimulation with HDND-12 in M1-like macrophages. More importantly, when we taken AG490 (inhibitor of JAK2/STAT3 signaling), the protein levels of iNOS were significantly reduced in AG490 stimulation group compare with control in LPS, IFN-γ and HDND-12 stimulation cells. Taken together, these findings indicated that HDND-12 could prevent polarization toward M1-like macrophages, at least in part, through modulating JAK2/STAT3 pathway.
Animals ; Cytokines ; genetics ; metabolism ; Enzyme Inhibitors ; pharmacology ; Gene Expression Regulation ; drug effects ; Hesperidin ; chemistry ; pharmacology ; Inflammation ; genetics ; metabolism ; Janus Kinase 2 ; antagonists & inhibitors ; metabolism ; Macrophages ; drug effects ; immunology ; metabolism ; Medicine, Chinese Traditional ; Mice ; Molecular Structure ; Phosphorylation ; drug effects ; RAW 264.7 Cells ; STAT3 Transcription Factor ; antagonists & inhibitors ; metabolism ; Signal Transduction ; drug effects

To analyze the efficacy and compliance of conventional immunotherapy(CIT)and rush immunotherapy(RIT)in patients with allergic rhinitis.This trial was a prospective study involved 404 patients with persistent AR who were allergic to house dust mite.328 patients were assigned to the conventional immunotherapy reaching the maintenance dose within 14 weeks,and 76 patients were assigned to the rush immunotherapy reaching the maintenance dose within 1 week.The visual analog scale(VAS)score and the patients' compliance were recorded during treatment and follow-up.After CIT and RIT,the VAS score were significantly reduced in each group,but the decrement of VAS score of RIT group was more evident than that of CIT in half ayear(<0.05).After 5 years follow-up,the VAS score of two groups was also significantly reduced.The rate of treatment continuation of CIT group in 1 year,2 years and 3 years were 18.5%,39.0% and 57.3%,higher than RIT group(11.8%,26.3%,42.1%),respectively.Both CIT and RIT were beneficial for allergic rhinitis patients,and the clinical efficacy lasts for at least 5 years.But RIT has the superiority of faster onset and better compliance.
Allergens ; Animals ; Dermatophagoides pteronyssinus ; Desensitization, Immunologic ; Humans ; Immunotherapy ; Patient Compliance ; Prospective Studies ; Pyroglyphidae ; Rhinitis, Allergic ; therapy ; Treatment Outcome

Traditional Chinese medicine(TCM) pill, the most representative and successive dosage form, is called as one of the four classical TCM dosage forms. "Pills could keep the lasting and lenitive therapeutic efficacy for a long period" is the most classical dosage form theory, showing a guidance significance in making recipe, preparations and clinic application. In this article, we would elucidate the inheritance and development significance of TCM pills in three key points, including dosage form theory, pharmaceutical preparation technology and clinic usage based on the pharmaceutics connotation of this theory. From this, it can provide the basis for researches on pills mechanism, material basis and mode of action in clinical application.

AIM:To investigate the effect of Eph receptor A2 (EphA2) on drug resistance of colorectal carci-noma cells and its possible mechanisms .METHODS:Real-time PCR and Western blot were used to detect the expression of EphA2 at mRNA and protein levels in LoVo and LoVo/5-FU cells.EphA2 siRNA was transfected to down-regulate the EphA2 expression in LoVo/5-FU cells, and the drug sensitivity was calculated by CCK-8 assay.Meanwhile, cell migration and invasion were measured by wound healing assay and Transwell assay , and the protein levels of E-cadherin,β-catenin, N-cadherin, vimentin, Notch and Snail were determined by Western blot .RESULTS: The expression of EphA2 at both mRNA and protein levels was significantly up-regulated in LoVo/5-FU cells (P<0.05).Knockdown of EphA2 suppressed the cell viability, and migration and invasion abilities , but promoted drug sensitivity of LoVo/5-FU cells.Up-regulation of E-cadherin and β-catenin, and down-regulation of N-cadherin and vimentin were observed , indicating that the epithelial-mesenchymal transition ( EMT) process was suppressed .Knockdown of EphA2 decreased the expression levels of Notch and Snail.CONCLUSION:Down-regulation of EphA2 partly reverses drug resistance of LoVo/5-FU cells.The mechanism may be related to suppressing cell growth , migration, invasion and EMT process via Notch/Snail signaling pathway .

Objective To analyze the genotypes and homology of MSP?1 and CSP gene of Plasmodium vivax in Shandong Province,so as to provide the evidence for case traceability. Methods A total of 12 blood samples were collected from P. vivax?infected cases in Shandong Province in 2011. Parasite genomic DNA was extracted. Primers were designed according to MSP?1 and CSP gene sequences of P. vivax. Then Nested PCR,enzyme digestion,sequencing and sequence alignment,and homolo?gous analysis were performed. Results The MSP?1 gene of all the 12 samples from P. vivax?infected cases were detected with a 470 bp PCR amplification band,and 350 bp and 120 bp enzyme digestion fragments,which were identified as type Sal?1. An analysis of phylogenetic tree of MSP?1 gene showed that the sequences of 9 indigenous case samples in Shandong Province were located in the same branch,one case sample infected from India was located in the same branch with India strains. All the 12 P. vivax?infected samples covered GDRA(D/A)GQPA sequences in CSP gene,which were identified as type PV?Ⅰ. Of the CSP gene among 12 P. vivax?infected samples,10 samples of indigenous case in Shandong Province and one sample of the case in?fected in Guangdong Province were detected with both 560-840 bp and 150-230 bp PCR amplification bands,which were iden?tified as temperate zone family strain of type PV?Ⅰ. However,one sample from the case infected in India was detected only with a 560-840 bp band,which was identified as tropical zone family strain of PV?Ⅰ. An analysis of phylogenetic tree of CSP gene showed that the sequences of 10 samples from the indigenous cases in Shandong Province and one sample from the case infected in Guangdong Province were located in the same branch,one sample from the case infected in India was located in the same branch with India and Indonesia strains. Conclusion Of all the indigenous isolates in Shandong Province,MSP?1 gene is geno?typed type Sal?1,CSP gene is genotyped temperate zone family strain of type PV?Ⅰ,with a high homology found among the in?digenous isolates.

The present study was designed to examine the anti-hyperuricemic and anti-inflammatory effects and possible mechanisms of vaticaffinol, a resveratrol tetramer isolated from ethanol extracts of Dipterocarpus alatus, in oxonate-induced hyperuricemic mice. At 1 h after 250 mg·kg potassium oxonate was given, vaticaffinol at 20, 40, and 60 mg·kg was intragastrically administered to hyperuricemic mice once daily for seven consecutive days. Vaticaffinol significantly decreased serum uric acid levels and improved kidney function in hyperuricemic mice. It inhibited hepatic activity of xanthine dehydrogenase (XDH) and xanthine oxidase (XOD), regulated renal mRNA and protein levels of urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporter 1 (OAT1), organic cation transporter 1 (OCT1), OCT2, organic cation/carnitine transporter 1 (OCTN1), and OCTN2 in hyperuricemic mice. Moreover, vaticaffinol markedly down-regulated renal protein levels of NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like (ASC), and Caspase-1, resulting in the reduction of interleukin (IL)-1β, IL-18, IL-6 and tumor necrosis factor-α (TNF-α) levels in this animal model. Additionally, HPLC and LC-MS analyses clearly testified the presence of vaticaffinol in the crude extract. These results suggest that vaticaffinol may be useful for the prevention and treatment of hyperuricemia with kidney inflammation.
Animals ; Anti-Inflammatory Agents ; administration & dosage ; Dipterocarpaceae ; chemistry ; Humans ; Hyperuricemia ; blood ; drug therapy ; immunology ; Interleukin-18 ; genetics ; immunology ; Interleukin-1beta ; genetics ; immunology ; Interleukin-6 ; genetics ; immunology ; Kidney ; drug effects ; immunology ; Male ; Mice ; Organic Anion Transport Protein 1 ; genetics ; immunology ; Plant Extracts ; administration & dosage ; Stilbenes ; administration & dosage ; Tumor Necrosis Factor-alpha ; genetics ; immunology ; Uric Acid ; blood