Objective: To clarify the specific mechanisms of action of raw Phellodendron chinense Schneid. (RPC) and saltwater-processed PC (SPC) in the treatment of rats with a kidney-yin deficiency pattern (KYDP). Methods: Healthy rats were administered hydrocortisone to establish a KYDP model. The rats were divided into seven groups: blank control, model, positive control (Liuwei Dihuang pills), high-dose RPC, low-dose RPC, high-dose SPC, and low-dose SPC. Enzyme-linked immunosorbent assay was used to measure the levels of cAMP, cGMP, TRH, TSH, T3, T4, IFN-γ, TNF-α, and testosterone in the serum and the levels of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in the liver. TRH mRNA expression in the rat hypothalamus was measured using RT-PCR. THRα1+2 protein expression in the hypothalamus of rats was measured using Western blot. Immunohistochemistry was performed to determine the expression levels of FAS, FasL, and TSHR. Flow cytometry was used to determine CD4+ and CD8+ T lymphocyte levels. Illumina MiSeq sequencing technology was used to evaluate the diversity of intestinal flora in KYDP rats. Results: The cAMP/cGMP ratio was significantly higher in the model group than in the blank control group (P = .048). Compared with the model group, after administration, the levels of the above-mentioned serum and liver indexes decreased, except that of testosterone. The CD4+/CD8+ ratio also decreased. Compared with the RPC group, the levels of T3, IFN-γ, FAS, FasL, and TSHR in the SPC group decreased whereas that of testosterone increased. Additionally, immune function and intestinal flora diversity improved in the SPC group. SPC proved to be more effective in improving liver energy metabolism in KYDP rats than RPC. Conclusion SPC had a better therapeutic effect on KYDP than RPC. The underlying mechanism of action may be related to improvements in liver energy metabolism, immune function, and intestinal flora diversity.

Objective To explore whether voluntary wheel running affects liver oxidative stress by regulating the Nrf2/HO-1 pathway,thereby alleviating HFFC diet-related lipid deposition in the liver.Methods Eight-week-old C57BL/6J mice were randomly divided into a normal diet group(NC group,n=10)and high-fat,fructose,and cholesterol diet group(HFFC group,n=20)after 1 week of adaptive feeding.Ten weeks of feeding later,mice in the HFFC group were divided into a quiet group(HFFC group,n=10)and HFFC combined with exercise group(HFFC+EX group,n=10).HFFC+EX group mice were caged with voluntary running wheels for free movement,and the number of running wheels was recorded every day for 8 weeks.After the last treatment,the mice were sacrificed by fasting for 12 hours at an interval of 24 hours,and the blood and liver were collected for analysis.Results(1)Body weight,liver weight,and liver index of mice fed the HFFC diet were significantly higher than those of the NC group,which significantly decreased after exercise(P＜0.05).(2)Compared with the NC group,HDL-C and LDL-C in the HFFC group were significantly increased,and the LDL-C level was significantly decreased after 8 weeks of exercise(P＜0.05).(3)The liver fat droplet area and liver TG content in the HFFC group were significantly higher than those in the NC group,whereas those in HFFC+EX group were significantly decreased(P＜0.05).(4)Compared with the NC group,the content of oxidase MDA in the HFFC group were significantly increased,and nuclear translocation and gene expression of Nrf2 were significantly decreased.After exercise,the activities of SOD and T-AOC were significantly increased,and the nuclear translocation and gene expression of Nrf2 and expression levels of HO-1 and SOD-1 were significantly increased(P＜0.05).(5)The number of apoptotic hepatocytes and CHOP expression in the HFFC diet group were significantly higher than those in the NC group,whereas the number of apoptotic hepatocytes,and CHOP and Bax/Bcl-2 expression in the exercise group were significantly lower than those in the NC group(P＜0.05).Conclusions Voluntary wheel can alleviate HFFC diet induced liver lipid deposition by regulating the Nrf2/HO-1 pathway,thereby alleviating oxidative stress and reducing apoptosis in liver cells.

Objective:To observe any effect of combining electro-acupuncture with aerobic exercise on the expression of SR-BI receptor and caveolin-1 and ABCA1 proteins in the liver and on reverse cholesterol transport. Any relationship with inflammatory factors NF-κBp65, COX-2 and TNF-α in the aortic arch was also investigated.Methods:Thirty male SPF Sprague-Dawley rats were randomly divided into a normal group (NG), a model group (MG), and a group which received electro-acupuncture combined with aerobic exercise (the EAG group), each of 10. A hyperlipidemia model was induced in the rats of the MG and EAG groups by feeding a high-fat diet. For 4 weeks the EAG group received 30 minutes of electroacupuncture daily (frequencies of sparse/dense waves 2/100Hz, 1mA) at the ST40 and SP9 acupoints, followed by 60 minutes of no weight bearing swimming. No intervention was applied to the other groups. Before and after the intervention, serum was collected to observe lipid levels. Liver and aortic arch issue were resected to measure lipid deposition and inflammation using hematoxylin eosin staining. Caveolin-1, SR-BI and ABCA1 in the liver and NF-κBp65, COX-2 and TNF-α in the aortic arch were quantified using real-time PCRs and western blotting.Results:After successful modeling the levels of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), and the protein and mRNA expressions of NF-κBp65, TNF-α, COX-2 and COX-2 in the aortic arches of the MG had increased significantly. High density lipoprotein cholesterol (HDL-C) and the protein and mRNA expressions of caveolin-1, SR-BI and ABCA1 in the liver had decreased significantly. Compared with the MG, the levels of TC and LDL-C, as well as the protein and mRNA expressions of NF-κBp65, TNF-α, COX-2 and COX-2 in the aortic arches of the EAG had decreased significantly, while the average HDL-C l level, as well as the protein and mRNA of caveolin-1, SR-BI and ABCA1 in the liver were up-regulated significantly.Conclusions:Electroacupuncture combined with aerobic exercise can relieve hyperlipidemia through promoting cholesterol reverse transport and inhibiting inflammation in endothelial cells. Those effects may be related to up-regulating the expression of caveolin-1, SR-BI and ABCA1 in the liver and down-regulating inflammatory factors in the aortic arch.

Objective:To investigate the risk factors for hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS), and the predictive value of Neutrophil to lymphocyte ratio (NLR).Methods:Consecutive patients with AIS received IVT in Zhengzhou People’s Hospital from January 2021 to December 2022 were retrospectively enrolled. HT was defined as no intracranial hemorrhage was found on the first imaging examination after admission, and new intracranial hemorrhage was found on the imaging examination 24 h after IVT or when symptoms worsened. sHT was defined as HT and the National Institutes of Health Stroke Scale (NIHSS) score increased by ≥4 compared to admission or required surgical treatment such as intubation and decompressive craniectomy. The baseline clinical and laboratory data of the patients were collected, and NLR, lymphocyte to monocyte ratio (LMR), and platelet to neutrophil ratio (PNR) were calculated. Multivariate logistic regression analysis was used to identify the independent predictors of HT and sHT, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of NLR for HT and sHT after IVT. Results:A total of 196 patients were included (age 65.37±13.10 years, 124 males [63.3%]). The median baseline NIHSS score was 4 (interquartile range: 2-10). Twenty patients (10.2%) developed HT, and 12 (6.1%) developed sHT. Univariate analysis showed that there were statistically significant differences in age, baseline NIHSS score, creatinine, NLR, and stroke etiology type between the HT group and the non-HT group (all P<0.05); there were statistically significant differences in age, NLR, PNR, creatinine, baseline NIHSS score, and stroke etiological type between the sHT group and the non-sHT group (all P<0.05). Multivariate logistic regression analysis showed that NLR was an independent predictor of HT (odds ratio [ OR] 1.375, 95% confidence interval [ CI] 1.132-1.670; P=0.001) and sHT ( OR 1.647, 95% CI 1.177-2.304; P=0.004) after IVT. The ROC curve analysis showed that the area under the curve for predicting HT by NLR was 0.683 (95% CI 0.533-0.833; P=0.007), the optimal cutoff value was 5.78, the sensitivity and specificity were 55.0% and 84.1%, respectively. The area under the curve for predicting sHT by NLR was 0.784 (95% CI 0.720-0.839; P=0.001), the optimal cutoff value was 5.94, the sensitivity and specificity were 66.67% and 84.24%, respectively. Conclusions:A higher baseline NLR is associated with an increased risk of HT and sHT after IVT in patients with AIS, and can serve as a biomarker for predicting HT and sHT after IVT.

Because the work of administrative and logistics personnel in public hospitals is difficult to quantify and evaluate, its performance reform is difficult. A large public hospital in Wuhan has explored and established a distribution incentive mechanism that combines department performance appraisal, individual classification and grading, and secondary distribution within the department. Taking into account the completion of performance appraisal indicators of the national tertiary public hospital in the department, the results of the institutional " Excellent Management Team Ranking" , personal job grades, working years and other factors, a relatively mature and operable system has been formed, which could provide reference for the performance reform of other hospitals.

Objective:To investigate the prognostic value of infarct size (IS) in patients with acute ST-segment elevation myocardial infarction (STEMI) underwent primary percutaneous coronary intervention (PCI).Methods:A total of 104 patients with acute STEMI who underwent primary PCI treatment in Shengjing Hospital of China Medical University from February 2017 to November 2018 were included in the present study. All patients underwent cardiovascular magnetic resonance (CMR) within one week after primary PCI treatment. The subjects were followed up for two years. Major adverse cardiac events (MACE) included new onset congestive heart failure and/or recurrent nonfatal myocardial infarction and/orcardiac death. The optimal IS cutoff value for MACE was determined by receiver operating character (ROC) curve. Based on the IS cutoff value, the patients were divided into the high IS group and the low IS group. Clinical characteristics between the two groups were compared. A cox regression model was used to analyze the prognostic value of IS in acute STEMI patients treated with primary PCI for the adverse events.Results:The IS cutoff value determined by ROC curve was 13.55%. 50 patients were in the high IS group (IS≥13.55%) and 54 patients were in the low IS group (IS<13.55%). More female patients [14 cases (28.0%) vs. 6 cases (11.1%)] were in the IS group, and a higher proportion of patients in the high IS group had anterior myocardial infarction [27 cases (54.0%) vs. 16 cases (29.6%)] or microvascular obstruction [32 cases (64.0%) vs. 16 cases (29.6%)]. White blood cell counts [11.25(8.90, 13.38) ×10 9/L vs. 9.25(7.58, 11.00) ×10 9/L], troponin I levels [50.63(16.56, 76.30)μg/L vs. 16.58(2.66, 38.42)μg/L] and brain natriuretic peptide levels [178.10(79.70, 281.95)μg/L vs. 79.60(42.83, 183.90)μg/L] in the high IS group were higher than those in the low IS group ( P<0.05), and left ventricular ejection fraction [(45.15±10.65)% vs. (51.95±12.91)%] in the high IS group was lower than that in the low IS group ( P<0.05). Multivariate Cox regression analyses showed that IS was independently associated with the risk of cardiac death in patients with acute STEMI two years after primary PCI( P=0.033, HR=1.075, 95% CI1.006-1.148). Every 1% increase in IS was associated with a 7.5% increase in cardiac death. Conclusions:Infarct size, measured by CMR within one week after primary PCI, is strongly associated with cardiac death in patients with acute STEMI two years after primary PCI. IS could be used as an index for the prognosis of patients with acute STEMI.

Dabigatran etexilate mesylate(DE)and tadalafil(TD)are BCS class II drugs with poor water solubility. 〓 In this study coamorphization technique was used to improve their solubilities/dissolutions and hence to enhance their oral absorptions. The coamorphous DE-TD were prepared by solvent-evaporation method and characterized by PXRD, DSC, FTIR and TGA. In addition, dissolution behavior and physical stability were also investigated. Only halo pattern and a single Tg of 119 °C was observed on the PXRD and DSC of the co-evaporated product, respectively, indicating the formation of coamorphous DE-TD. FTIR result suggested that a hydrogen bond was probably formed between N-H group of DE and C==O group of TD. In comparison to crystalline counterparts, coamorphous DE-TD showed a significantly improved intrinsic dissolution rate and prolonged supersaturation time in intrinsic dissolution and supersaturation dissolution studies, respectively. No crystallization was observed under affecting factors testing(30 days)as well as long-term and accelerated stability testing(90 days)for the prepared coamorphous DE-TD under 25°C/60%RH or 40°C/75%RH, while amorphous DE crystalized at 10 days under 25 ℃/75% RH.

Objective To study the effect of deep inspiration breath-hold(DIBH)technique on the heart dose in whole breast irradiation(WBI)for left breast cancer after breast-conserving surgery, and to investigate the anatomical factors for heart dose. Methods Fifteen patients with left breast cancer who received WBI after breast-conserving surgery and met breathing control requirements were prospectively enrolled as subjects. Simulated CT scans were performed during free breathing(FB)and DIBH. The WBI plans were optimized based on DIBH images.The position,volume,and radiation doses to the heart and lung were compared between the status of FB and DIBH. Correlation of heart dose with various anatomical factors was analyzed in FB status. Between-group comparison of categorical data was made by nonparametric Wilcoxon rank test.A two-variable correlation analysis was made by the Pearson method.Results There was no significant difference in heart volume between the status of FB and DIBH(P=0.773).The volume of both lungs was significantly larger in DIBH status than in FB status(P=0.001). The mean and maximum doses and V5-V40for the heart,left anterior descending coronary artery,left ventricle,right ventricle,and left lung were significantly lower in DIBH status than in FB status(all P<0.05). The greater DIBH increased the lung volume,the greater the mean heart dose decreased. In FB status,the left breast volume,heart-to-lung volume ratio,distance between the inferior margins of breast and heart,and maximum heart margin distance showed a linear correlation with heart dose. Particularly, the heart-to-lung volume ratio and maximum heart margin distance were independently correlated with heart dose. Conclusions DIBH technique in WBI for left breast cancer after breast-conserving surgery significantly reduces heart and lung doses compared with FB. Changes in lung volume are the basis for improving the relative anatomical location of the heart. The heart-to-lung volume ratio and maximum heart margin distance may provide a reference for DIBH technique.

Objective To observe the effect of heat needle treatment on the inflammatory reaction in the damaged tissues of rats with the third lumbar transverse process syndrome. Methods Ninety Sprague-Dawley rats were randomly divided into 6 groups, namely normal group, model group, drug group, heat needle group, conventional acupuncture group and warming acup-moxibustion group, 15 rats in each group. The rat model of the third lumbar syndrome was established by embedding gelatin sponge. Two weeks later, the rats in various groups were given corresponding treatment respectively. Before treatment and on the 7th, 14th and 28th day of treatment, the blood samples were collected from jugular vein, and then the serum inflammatory cytokines of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). On the 28th day of treatment, all of the rats were sacrificed, the expression levels of TNF-α, IL-1βand IL-6 mRNA in the muscle tissue were detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), and the pathological changes in local muscle tissue were observed by HE staining method. Results The serum contents of the inflammatory cytokines of TNF-α, IL-1β and IL-6 in the model group and treatment groups after modeling were significantly higher than those in the normal group (P < 0.05). After treatment, the contents of TNF-α, IL-1β and IL-6 in various treatment groups were decreased significantly as compared with those in the model group, and the decrease was most obvious in the heat needle group. The expression levels of TNF-α, IL-1β and IL-6 mRNA in muscle tissues of drug group, heat needle group, conventional acupuncture group and warming acup-moxibustion group were lower than those of the model group (P < 0.05), and the heat needle group had the lowest levels. HE staining results showed that heat needle group had milder inflammatory reaction and better muscle fiber structure than the model group. Conclusion Heat needle treatment can improve the local inflammatory response and promote the repair of tissue damage through decreasing the expression levels of inflammatory cytokines of TNF-α, IL-1βand IL-6.

Rhamnolipid biosurfactant is mainly produced by Pseudomonas aeruginosa that is the opportunistic pathogenic strain and not suitable for future industrial development. In order to develop a relatively safe microbial strain for the production of rhamnolipid biosurfactant, we constructed engineered Escherichia coli strains for rhamnolipid production by expressing different copy numbers of rhamnosyltransferase (rhlAB) gene with the constitutive synthetic promoters of different strengths in E. coli ATCC 8739. We further studied the combinatorial regulation of rhlAB gene and rhaBDAC gene cluster for dTDP-1-rhamnose biosynthesis with different synthetic promoters, and obtained the best engineered strain-E. coli TIB-RAB226. Through the optimization of culture temperature, the titer of rhamnolipd reached 124.3 mg/L, 1.17 fold higher than that under the original condition. Fed-batch fermentation further improved the production of rhamnolipid and the titer reached the highest 209.2 mg/L within 12 h. High performance liquid chromatography-mass spectrometry (LC-MS) analysis showed that there are total 5 mono-rhamnolipid congeners with different nuclear mass ratio and relative abundance. This study laid foundation for heterologous biosynthesis of rhanomilipd.
Bacterial Proteins ; genetics ; Batch Cell Culture Techniques ; Decanoates ; Escherichia coli ; metabolism ; Fermentation ; Glycolipids ; biosynthesis ; Hexosyltransferases ; genetics ; Industrial Microbiology ; methods ; Multigene Family ; Promoter Regions, Genetic ; Pseudomonas aeruginosa ; Rhamnose ; analogs & derivatives ; biosynthesis ; Surface-Active Agents ; metabolism