Objective: The docking and superantigen activity sites of staphylococcal enterotoxin-like W (SElW) and T cell receptor (TCR) were predicted, and its SElW was cloned, expressed and purified. Methods: AlphaFold was used to predict the 3D structure of SElW protein monomers, and the protein models were evaluated with the help of the SAVES online server from ERRAT, Ramachandran plot, and Verify_3D. The ZDOCK server simulates the docking conformation of SElW and TCR, and the amino acid sequences of SElW and other serotype enterotoxins were aligned. The primers were designed to amplify selw, and the fragment was recombined into the pMD18-T vector and sequenced. Then recombinant plasmid pMD18-T was digested with BamHⅠand Hind Ⅲ. The target fragment was recombined into the expression plasmid pET-28a(+). After identification of the recombinant plasmid, the protein expression was induced by isopropyl-beta-D- thiogalactopyranoside. The SElW expressed in the supernatant was purified by affinity chromatography and quantified by the BCA method. Results: The predicted three-dimensional structure showed that the SElW protein was composed of two domains, the amino-terminal and the carboxy-terminal. The amino-terminal domain was composed of 3 α-helices and 6 β-sheets, and the carboxy-terminal domain included 2 α-helices and 7 antiparallel β-sheets composition. The overall quality factor score of the SElW protein model was 98.08, with 93.24% of the amino acids having a Verify_3D score ≥0.2 and no amino acids located in disallowed regions. The docking conformation with the highest score (1 521.328) was selected as the analysis object, and the 19 hydrogen bonds between the corresponding amino acid residues of SElW and TCR were analyzed by PyMOL. Combined with sequence alignment and the published data, this study predicted and found five important superantigen active sites, namely Y18, N19, W55, C88, and C98. The highly purified soluble recombinant protein SElW was obtained with cloning, expression, and protein purification. Conclusions: The study found five superantigen active sites in SElW protein that need special attention and successfully constructed and expressed the SElW protein, which laid the foundation for further exploration of the immune recognition mechanism of SElW.
Humans ; Enterotoxins/genetics* ; Superantigens/genetics* ; Catalytic Domain ; Selenoprotein W/metabolism* ; Receptors, Antigen, T-Cell

Objective The recurrence rate of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA) remains relatively high. The aim of this study was to investigate the predictive value of rs2200733 polymorphism for AF recurrence after RFCA. Methods Fifty-three AF patients underwent RFCA guided by the magnetic navigation system between July 2015 and September 2016 in Wuxi People’s Hospital. We obtained the baseline data on the patients, conducted genotyping for rs2200733 variants, and followed up the patients for symptoms and complications by electrocardiography (ECG) and dynamic ECG. Using Cox survival analysis, we determined the independent predictors of AF recurrence after RFCA and the sensibility and specificity of predicting AF recurrence at 12 and 24 months post-operatively. Results All the patients were Han Chinese, followed-up for 21.6 ± 9.5 months, and 25 (47.2%) of them experienced AF recurrence at 6.6 ± 5.3 months after RFCA. Kaplan-Meier survival analysis revealed a significant association between rs2200733 polymorphism and AF recurrence in the additive and recessive models (P < 0.001), and multivariate Cox analysis showed the rs2200733 polymorphism (recessive model) to be an independent predictor of post-RFCA AF recurrence (OR = 3.184, 95% CI: 1.378-7.357, P = 0.007). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of rs2200733 TT in predicting AF recurrence at 12 months were 64%, 81%, 70%, 76% and 74%, and those at 24 months were 60%, 82%, 75%, 70%, and 72%, respectively. Conclusion The rs2200733 polymorphism is an independent predictor of AF recurrence after RFCA, and its high specificity indicates that it could be used as a tool for screening Han Chinese patients with AF for RFCA.

Adult ; Apolipoproteins E ; genetics ; Asian Continental Ancestry Group ; Exons ; genetics ; Female ; Humans ; Kidney Diseases ; genetics ; Mutation ; genetics ; Young Adult

Objective The mechanisms of docosahexaenoic acid (DHA) protecting the cardiovascular system have not yet been clarified. This study was to investigate the vasorelaxative effect of 13,14-epoxy docosapentaenoic acid (13,14-EpDPE) on coronary arterioles in normal rats and its action mechanisms.Methods We isolated coronary artery smooth muscle cells (CASMCs) from normal rats by enzyme digestion, examined the open probabilities of the large conductance calcium-activated potassium (BK) channels in inside-out single channel configuration in the presence of different concentrations (0, 1, 10 and 100 pmol/L) of 13,14-EpDPE, and recorded the BK currents with the patch clamp in whole cell configuration. Then we assessed the coronary arterial relaxation by measuring dilatory responses to 13,14-EpDPE in pre-contracted tissues with or without pre-treatment with iberiotoxin.Results In the presence of 0, 1, 10 and 100 pmol/L of 13,14-EpDPE, the open probabilities of the BK channels were 0.25±0.03, 0.34±0.03, 0.44±0.06 and 0.85±0.16 (n=6), respectively, significantly increased at 100 pmol/L as compared with 0, 1 and 10 pmol/L (P<0.05). The BK channels were activated by 13,14-EpDP in a concentration-dependent manner and its half-effect concentration was (15.94±1.21) pmol/L. The current density was increased from (58.27±16.35) to (95.94±23.00) pA/pF (P=0.002) after 10 pmol/L 13,14-EpDP perfusion when the stimulation voltage was 100 mV. 13,14-EpDPE dilated the isolated coronary arterioles in a dose-dependent manner, and its effects were abolished after pre-treatment with iberiotoxin (100 nM).Conclusion 13,14-EpDPE can dilate coronary arterioles by activating BK channels in CASMCs, which might be one of the mechanisms underlying its protective effect on the cardiovascular system.

Objective To explore prognosis and remission-related factors in lupus nephritis (LN) patients.Methods Patients diagnosed as LN by renal biopsy in Tongji Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology between Jan 1,2011 and July 31,2016 were enrolled.All related baseline clinical data was recorded and regular follow-up was performed.Kaplan-Meier curves was used to analyze partial remission and complete remission rates.Log-rank test was performed to compare remission rates of patients with nephrotic-range proteinuria (24-hour proteinuria≥3.5 g) and without nephrotic-range proteinuria (24-hour proteinuria＜3.5 g).Univariate and muhivariate Cox regression analyses were performed to evaluate the remission-related factors in different periods.Results A total of 115 patients,with 88.7％ female and (31.5±9.5)years mean age,were followed up for up to 5 years.During follow-up period 2 patients died and 1 dialyzed.The 6-,12-,24-and 36-and 48-month renal partial remission and complete remission rates were 33.3％,58.2％,71.5％,84.0％,89.6％,and 18.9％,40.5％,67.3％,79.4％,87.0％,respectively.Patients without nephrotic-range proteinuria had higher complete remission than patients with nephrotic -range proteinuria (HR=2.01,95％CI 1.15-3.34,P=0.014),but there was no difference in their partial remission (HR=1.33,95％ CI 0.74-2.43,P=0.341).Multivariate Cox regression model indicated that every 1 g/L increase in baseline level of serum albumin was associated with increased 8％ and 9％ risk,respectively,in partial remission (HR=1.08,95％CI 1.01-1.15,P=0.024) and complete remission (HR=1.09,95％CI 1.01-1.07,P=0.038).Conclusions Around half of LN patients reach remission during 1 year.Patients without nephrotic-range proteinuria have higher complete remission,and serum albumin is a remission-related factors.

Objective To evaluate the detection accuracy of the biomarkers dickkopf-1, DCP and AFP as a serum biomarker panel by comparing the sensitivity of the panel with those of the individual biomarkers. Methods The study was composed of three groups, one with HCC patients, one with non-HCC liver diseases and one with healthy controls. Serum AFP was measured using a chemiluminescence assay and serum dickkopf-1 and DCP were measured with ELISA. The sensitivity and specificity of the biomarkers were analyzed as single parameters and as a serum panel. Results The HCC group showed higher levels of dickkopf-1, DCP and AFP than the other two groups (P < 0.05). Dickkopf-1 showed better sensitivity (73.26% vs. 58.13%, P < 0.05) and better specificity (44.0% vs. 29.0%, P < 0.05) than AFP. DCP also had better sensitivity (74.42% vs. 58.13%, P < 0.05) than AFP, but their specificity was similar (30.00% vs. 29.00%, P > 0.05). The combination of the biomarkers as a serum panel produced much better sensitivity (93.02%) and specificity (78.00%) than each of the markers individually (P < 0.05). Conclusion The combination of AFP, DCP and dickkopf-1 as a biomarker panel can significantly improve the detection power with much higher sensitivity and specificity for HCC than any of the biomarkers alone. The tests are convenient and inexpensive, and may serve as a valuable addition to current options for the diagnosis of HCC.

Original missions: Aquatic therapy in Cheng Hsin General Hospital was founded specifically for patients with poliomyelitis in 1960s. At that time, Taiwan was shrouded in darkness due to the outbreak of polio. Many children were paralyzed overnight and thousands of families broke down. Desperate as they were, they had caught a glimmer of hope when the First Lady, Madam Chiang, decided to run a national shelter for children with polio. Cheng Hsin Children’s Home was built and involved in educational and medical systems to provide full time care for free. Aquatic therapy was also included at that time. Following Missions: After poliomyelitis being eradicated in Taiwan in 1983, our team was dedicated in aquatic rehabilitation for people with all kinds of disabilities. Since Taiwan National Health Insurance System being established in 1995, the population receiving rehabilitation kept on rising. As a pioneer in the field of aquatic therapy, we delivered our experience to assist in construction of aquatic rehabilitation nationwide. Learning from the numerous cases, we have accumulated much experience, especially neurological deficits. Thus, physical therapists in Cheng Hsin General Hospital have designed some treatment guidelines for neurological patients. These guidelines, though not standardized, provide therapists various aspects to evaluate clinical problems and to design programs (See Table). Further missions: From the polio to all kinds of special needs, aquatic therapy in Cheng Hsin General Hospital has prosperously developed. In order to broaden our horizon, our team is eager to joining international society of medical hydrology and adopting professional advices and collaboration.

  Hydrotherapy refers to therapy conducted in water. The most advanced aquatic therapy of all is the therapeutic swimming. Therapeutic swimming is to use swimming, with adjusted strokes and changed moves, as a fashion of treatment based on patients’ diagnosis. Almost everyone is indicated.   It’s much easier to those who already know how to swim. Making local adjustment of the strokes for special needs is all therapist has to do. For instance, a scoliosis case, having C curve at thoracic region with concave to left, can use modified breaststroke. By extending elbow during power phase, the muscles on upper back and shoulder can be recruited. These muscles are protectors of the thoracic spine. Freestyle stroke can be in use, too. The left hand enters the water when the arm reaches out to the farthest; in addition, the head rotates to the opposite side of the reaching hand. These movements can stretch and elongate the shortened side. As for the lengthened side, the right side, strengthening should be emphasized more. Hence, patients put their right hand on their sacrum. This is not only effective for upper back and shoulder strengthening, but also good for chest expansion.   However, the therapy won’t jump to therapeutic swimming for beginners. New patients usually start with basic exercise, for example, walking, marching, stretching, and strengthening. Therapeutic swimming is saved to the last. “Be friend with water” is the primary mission. The therapy cannot work until the patients feel at home in water. There are seven characteristics of water, which are buoyancy, hydrostatic pressure, resistance, visual feedback, audio feedback, and balance and coordination. All exercise programs are derived from the seven characteristics. Through thousands of times of practice, patients ought to be adapted to water, to like it, to know the benefits that they can gain from water. Most importantly, patients need to understand how safe they are in the water. The mean density of human is smaller than the density of water, which means patients can always float. Once they realize this fact, they should be able to embrace water and relax. It’s easy to move by pushing water toward the opposite direction they are heading to. After they learned the skills, staying in water becomes a joy instead of fear. Do remember, therapeutic swimming is never a pageant. Speed and stunts are not our emphasis.   Once they catch up the skills, therapeutic swimming is more than a rehabilitation program. It is a part of their life. It is something they are enjoy doing. Some patients are extraordinarily talented, and they will further perfect their performance. Moreover, they can seek for professional advice of contest rules, and the speeding skills from swimming coach. At this point, they might have the chance to attend Paralympics! Therapeutic swimming was initially a rehabilitation approach. Then, people with special needs find delight from it. It becomes their recreation. Finally, this advanced exercise will likely bring them to an international stage. Therapeutic swimming realizes their dreams to outshine!

Autophagy, an evolutionarily conserved lysosomal degradation process, has drawn an increasing amount of attention in recent years for its role in a variety of human diseases, such as cancer. Notably, autophagy plays an important role in regulating several survival and death signaling pathways that determine cell fate in cancer. To date, substantial evidence has demonstrated that some key autophagic mediators, such as autophagy-related genes (ATGs), PI3K, mTOR, p53, and Beclin-1, may play crucial roles in modulating autophagic activity in cancer initiation and progression. Because autophagy-modulating agents such as rapamycin and chloroquine have already been used clinically to treat cancer, it is conceivable that targeting autophagic pathways may provide a new opportunity for discovery and development of more novel cancer therapeutics. With a deeper understanding of the regulatory mechanisms governing autophagy, we will have a better opportunity to facilitate the exploitation of autophagy as a target for therapeutic intervention in cancer. This review discusses the current status of targeting autophagic pathways as a potential cancer therapy.
Antibiotics, Antineoplastic ; therapeutic use ; Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; drug effects ; genetics ; Beclin-1 ; Chloroquine ; therapeutic use ; Drug Discovery ; Humans ; Membrane Proteins ; metabolism ; Molecular Targeted Therapy ; Neoplasms ; metabolism ; pathology ; therapy ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; metabolism ; Signal Transduction ; Sirolimus ; therapeutic use ; TOR Serine-Threonine Kinases ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

Objective To investigate the changes of open probability (Po) of large conductance Ca2+ -activated K + channel (BK channel ) in diabetic coronary smooth muscle cells and elucidate the underlying cellular electrophysiology mechanisms of coronary dysfunction.Methods Rat coronary smooth muscle cells were isolated from control group and diabetic group.BK single channel currents were recorded by patch clamp technique in inside-out configuration.Open probabilities were calculated and compared between two groups.After exposure to DHS-1,a specific BK channel activator,Po at 0.2 and 1 μmoL/L free Ca2+ were compared between control and diabetic groups.Results In the presence of 0.2 μmol/L free Ca2+,the Po at baseline was significantly lower in diabetic rats than in control rats (0.0032 ± 0.0012 vs.0.095 ±0.036,P ＜ 0.05).Cytoplasmic application of DSH-1 significantly increased the Po to 0.335 ±0.096 (P ＜0.05 vs.baseline) in control rats,whereas DSH-1 had no effect in diabetic rats ( Po =0.022 ±0.018,P＞0.05 vs.baseline).In the presence of 1 μmol/L free Ca2+,the Po at baseline was also significantly lower in diabetic rats than in control rats (0.210 ± 0.055 vs.0.458 ± 0.077,P ＜ 0.05 ).Cytoplasmic application of DHS-1 further robustly enhanced Po to 0.823 ± 0.019 (P ＜ 0.05 vs.baseline) in control rats and to 0.446 ± 0.098 in diabetic rats ( P ＜ 0.05 vs.baseline of diabetic rats; P ＜ 0.05 vs.control rats with DHS-1 ).Conclusion The decrease of Po of BK single channel in coronary smooth muscle cells may be a potential cause for coronary dysfunction in diabetic rats.