Study on construction of c-Met specific CAR-T cells and its killing effect on non-small cell lung carcinoma / 中华肿瘤杂志

Objective: To produce chimeric antigen receptor T cells (CAR-T) targeting human hepatocyte growth factor/c-Met (HGF/c-Met) protein and detect its cytotoxicity against non-small cell lung cancer (NSCLC) cells H1975 in vitro. Methods: The whole gene sequence of c-Met CAR containing c-Met single-chain fragment variable was synthesized and linked to lentiviral vector plasmid, plasmid electrophoresis was used to detect the correctness of target gene. HEK293 cells were transfected with plasmid and the concentrated solution of the virus particles was collected. c-Met CAR lentivirus was transfected into T cells to obtain second-generation c-Met CAR-T and the expression of CAR sequences was verified by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, and the positive rate and cell subtypes of c-Met CAR-T cells were detected by flow cytometry. The positive expression of c-Met protein in NSCLC cell line H1975 was verified by flow cytometry, and the negative expression of c-Met protein in ovarian cancer cell line A2780 was selected as the control. The cytotoxicity of c-Met CAR-T to H1975 was detected by lactate dehydrogenase (LDH) cytotoxicity assay at 1∶1, 5∶1, 10∶1 and 20∶1 of effector: target cell ratio (E∶T). Enzyme-linked immunosorbent assay (ELISA) was used to detect the release of cytokines such as TNF-α, IL-2 and IFN-γ from c-Met CAR-T co-cultured with H1975. Results: The size of band was consistent with that of designed c-Met CAR, suggesting that the c-Met CAR plasmid was successfully constructed. The results of gene sequencing were consistent with the original design sequence and lentivirus was successfully constructed. CAR molecules expression in T cells infected with lentivirus was detected by western blot and RT-qPCR, which showed c-Met CAR-T were successfully constructed. Flow cytometry results showed that the infection efficiency of c-Met CAR in T cells was over 38.4%, and the proportion of CD8(+) T cells was increased after lentivirus infection. The NSCLC cell line H1975 highly expressed c-Met while ovarian cancer cell line A2780 negatively expressed c-Met. LDH cytotoxicity assay indicated that the killing efficiency was positively correlated with the E∶T, and higher than that of control group, and the killing rate reached 51.12% when the E∶T was 20∶1. ELISA results showed that c-Met CAR-T cells released more IL-2, TNF-α and IFN-γ in target cell stimulation, but there was no statistical difference between c-Met CAR-T and T cells in the non-target group. Conclusions: Human NSCLC cell H1975 expresses high level of c-Met which can be used as a target for immunotherapy. CAR-T cells targeting c-Met have been successfully produced and have high killing effect on c-Met positive NSCLC cells in vitro.

Clinical characteristics and microbiological tests analysis of 18 patients with Talaromyces marneffei infection / 中国热带医学

@#Abstract:Objective　To investigate the clinical characteristics and early diagnostic methods of patients with Talaromyces marneffei infection, so as to reduce the mortality of patients. Methods The clinical characteristics and microbiological analysis data including fungal culture, smear examination and mass spectrometry were collected from 18 patients with Talaromyces marneffei infection in the Department of Respiratory Medicine, Department of Tuberculosis, and Department of Critical Respiratory Medicine in Fuzhou Pulmonary Hospital from January 2017 to December 2021, and descriptive analysis was conducted. Results　All the 18 patients were confirmed to be infected with Talaromyces marneffei by conventional culture and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS). The main infection sites of 18 patients with Talaromyces marneffei infection were lungs and lymph nodes, and the patients were accompanied by clinical manifestations such as cough, sputum and fever. The imaging features such as patchy shadows, mediastinal lymph node shadows and nodular shadows were common. Microbiological testing showed a statistically significant difference between smear and culture with a higher positive culture rate (χ2=13.74, P<0.05). The positive rate of blood culture in microbiological test was 60.0% (9/15), the positive rate of bronchial lavage fluid culture was 26.7% (4/15), the positive rate of sputum culture was 5.6% (1/18), one case each of pus, bone marrow, pleural fluid and cerebrospinal fluid was positive for culture and the other cases were negative, one case of sputum and one case of pus were positive for smear and the rest were negative. Colony characteristics showed that the colony morphology was mycelial phase at 25 ℃, producing red pigment, and the branching pattern of the penicillus was seen microscopically as monoverticillate or biverticillate; At 35 ℃, the yeast phase appeared at the initial stage, and then the mycelium phase changed after 5-6 days; the yeast phase was observed at 37 ℃, and yeast-like cells were seen under the microscope. All 18 patients with Talaromyces marneffei infection got better after using antifungal drugs. Compared with non-HIV patients with Talaromyces marneffei infection, leukopenia and anemia were common in HIV patients with Talaromyces marneffei infection, and the differences were statistically significant (P<0.05). 　Conclusions The infection of Talaromyces marneffei can be divided into localized type and disseminated type, which usually invade the lungs, skin, lymph nodes and other places. The main manifestations of patients are fever, cough, phlegm and other atypical symptoms. At present, the diagnosis of Talaromyces marneffei infection is mostly based on the fungal culture test, and the application of MALDI-TOF MS method can effectively shorten the diagnosis time of Talaromycosis marneffei. Clinical characteristics combined with microbiological analysis provide an objective basis for early diagnosis of patients with Talaromyces marneffei infection, and timely use of antifungal therapy can improve the prognosis of patients.

Concomitant repair of moderate or less tricuspid regurgitation during mitral valve surgery improves early and mid-term prognosis of tricuspid valve and right heart function / 中国胸心血管外科临床杂志

@#Objective    To investigate the effect of concomitant tricuspid valve repair during mitral valve surgery on the early and mid-term prognosis of the tricuspid valve and right heart function in the patients with moderate or less tricuspid regurgitation. Methods    A retrospective study of 461 patients with mitral valve disease requiring cardiac surgery combined with moderate or less tricuspid regurgitation in our hospital from 2011 to 2014 was done. They were 309 males and 152 females with a median age of 53.00 (44.00, 60.00) years. According to whether they received tricuspid valve repair (Kay’s annuloplasty, DeVega’s annuloplasty or annular ring implantation), the patients were divided into a mitral valve surgery only group (a nTAP group, n=289) and a concomitant tricuspid valve repair group (a TAP group, n=172). At the same time, 43 patients whose tricuspid valve annulus diameter was less than 40 mm in the TAP group were analyzed in subgroups. Results    The median follow-up duration was 3.00 years (range from 0.10 to 9.30 years). There was no perioperative death. Three months after surgery, the anteroposterior diameter of the right ventricle in the TAP group was significantly improved compared with that in the nTAP group [–1.00 (–3.00, 1.00) mm vs. 0.00 (–0.20, 2.00) mm, P=0.048]. Three years after surgery, the improvement of right ventricular anteroposterior diameter in the TAP group was still significant compared with the nTAP group [–1.00 (–2.75, 2.00) mm vs. 2.00 (–0.75, 4.00) mm, P=0.014], and the patients in the TAP group were less likely to develop moderate or more tricuspid regurgitation (3.64% vs. 35.64%, P<0.001). Annuloplasty ring implantation was more effective in preventing regurgitation progression (P=0.044). For patients with a tricuspid annulus diameter less than 40 mm, concomitant tricuspid valve repair was still effective in improving the anteroposterior diameter of the right ventricle in the early follow-up (P=0.036). Conclusion     Concomitant tricuspid valve repair for patients with moderate or less tricuspid regurgitation during mitral valve surgery can effectively improve the tricuspid valve and right heart function in the early and mid-term after surgery. Annuloplasty ring implantation is more effective in preventing regurgitation progression. Patients whose tricuspid annulus diameter is less than 40 mm can also benefit from concomitant tricuspid repair.

Analysis of refractive parameters and theirs correlation with spherical equivalent in preschool children aged 3 to 6 years / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the distribution of refractive parameters and theirs correlation with spherical equivalent(SE)in preschool children aged 3 to 6 years, and evaluate the accuracy of each screening index in diagnosing refractive errors.METHODS: Cross-sectional study. A total of 791 preschool children, ranging from 3 to 6 years old, who consented to undergo mydriatic refraction were selected. Axial length(AL), corneal refractive power(K), and SE were measured after microcoria optometry and mydriatic optometry. Additionally, the corneal radius of curvature(CR)and the axial length/corneal radius of curvature(AL/CR)ratio were calculated.RESULTS: A total of 791 students participated in the study, out of which 400(50.6%)were male and 391(49.4%)were female. The mean values for AL, CR, AL/CR, and SE were 22.62±0.94mm, 7.81±0.29mm, 2.90±0.09, and +1.95±1.31D, respectively. AL, CR, and AL/CR increased with age. AL and CR were significantly higher in males than in females(all P&#x003C;0.001), while there was no statistically significant difference between AL/CR and SE in males and females(P=0.82, 0.19). The correlation coefficients of SE and AL/CR, AL and CR were -0.86, -0.50 and 0.16, respectively. The results of multiple linear regression analysis indicate that for each unit increase in AL/CR, there was a corresponding shift of 10.91 towards myopia in SE. The sensitivity of AL/CR in screening for myopia was 94.44%, with a specificity of 90.46% and a Youden index of 0.84. For screening myopia under microcoria optometry, the sensitivity was 100%, with a specificity of 66.09% and a Youden index of 0.66. The area under the curve was 0.967 and 0.809 when the ROC curves were plotted using AL/CR and AL as indicators for screening myopia, respectively.CONCLUSION: For large group screening activities where mydriatic optometry is not feasible, AL/CR is better for evaluating refractive status and identifying children with myopia and hyperopia reserve that are lower than normal for their age, compared to AL and microcoria optometry.

Effect of vascular endothelial growth factor-A165 on scleral remodeling of guinea pigs with form-deprivation myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of the intravitreal injection of vascular endothelial growth factor-A165(VEGF-A165)on the scleral remodeling of guinea pigs with form-deprivation myopia(FDM).METHODS: A total of 120 tricolor guinea pigs, aged three weeks, were randomly divided into 6 groups, with 20 in each group. The blank group did not undergo any intervention. In the FDM group, only the FDM model was established. In the phosphate buffer saline(PBS)group, 2.5 μL of PBS was injected into the vitreous cavity before establishing the FDM model. In the 1ng group, 5ng group, and 10ng group, VEGF-A165 was injected into the vitreous cavity at concentrations of 1, 5 and 10ng, respectively, before the establishment of the FDM model. The FDM model was established by covering the right eyes of guinea pigs with translucent balloons for 14d. The diopter and axial length of the right eyes were measured before and after covering. After 14d, the content of dopamine(DA)in retina was measured by high performance liquid chromatography. Additionally, the mRNA and protein expression levels of matrix metalloproteinase-2(MMP-2), tissue inhibitor of matrix metalloproteinase-2(TIMP-2), transforming growth factor(TGF)-β1, TGF-β2 and α-smooth muscle actin(α-SMA)in sclera were detected by reverse transcription polymerase chain reaction(RT-PCR)and Western blot.RESULTS: Before covering, there were no significant differences in the diopter and axial length of the right eyes of guinea pigs in all groups(P&#x003E;0.05). After 14d of modeling, when compared with the blank group, FDM group showed an increase in the degree of myopia in the right eye, a prolongation of the axial length, a decrease in the content of DA in the retina, and an increase in the expression of MMP-2, TGF-β2 and α-SMA in the sclera. Conversely, the expression of TIMP-2 and TGF-β1 were decreased(P&#x003C;0.01). However, in comparison to the FDM group, the degree of myopia in the 1ng, 5ng, and 10ng groups of guinea pigs decreased, the growth trend of axial length slowed, the content of DA in the retina increased, and the expression of MMP-2, TGF-β2 and α-SMA in the sclera decreased. Furthermore, the expression of TIMP-2 and TGF-β1 in the sclera increased(P&#x003C;0.01). As the concentration of intravitreal injection of VEGF-A165 increased, the degree of myopia in the right eye of guinea pigs gradually increased, and the axial length gradually prolonged. The content of DA in the retina gradually decreased, the expression of MMP-2, TGF-β2, and α-SMA in the sclera gradually increased, while the expression of TIMP-2 and TGF-β1 decreased gradually.CONCLUSION: Intravitreal injection of VEGF-A165 can increase the content of DA in the retina of FDM guinea pigs, affect the expression of MMP-2, TIMP-2, TGF-β1, TGF-β2 and α-SMA in the sclera, and inhibit scleral remodeling of guinea pigs. Notably, the VEGF-A165 at the concentration of 1ng showed the most significant efficacy.

Relation of weight change after twenty on subsequent diabetes risk / 中华内分泌代谢杂志

Objective:To explore the association between weight change from age 20 to middle age and diabetes risk.Methods:A total of 10 104 residents over 40 years old were recruited in Guangzhou. The final analysis data set is a cohort of 6 272 patients from the REACTION study. Quartile of weight changes from age 20 to middle-age was used as an independent variable to explore its association with newly diagnosed diabetes. Simple and multivariable logistic regression analysis were used to calculate OR and 95% CI. Results:The prevalence of newly diagnosed diabetes in study cohort was 15.7%. Weight changes from age 20 to middle-age was significantly higher in diabetes group( P<0.001). Logistic regression analysis found in general population and overweight people [24.0≤body mass index(BMI)<28.0 kg/m 2], after adjusting for gender, age, educational level, family history of diabetes, drinking, SBP, waist circumference, cholesterol, high-density lipoprotein-cholesterol(HDL-C), TG, ALT, AST, the risk of diabetes increased in line with the magnitude of weight change( P=0.081). While in group of lean, normal and obese adult, no significant association has been found. Conclusion:The risk of diabetes increased with weight change in general population and overweight people, indicating that weight change in adults after age of 20 was positively associated with diabetes. It is suggested the importance of weight management in the prevention of dialetes.

Identification of traditional Chinese drugs containing active ingredients for treating myocardial infarction and analysis of their therapeutic mechanisms by network pharmacology and molecular docking / 南方医科大学学报

OBJECTIVE@#To identify traditional Chinese drugs that contain active ingredients for treatment of myocardial infarction (MI) and explore their therapeutic mechanisms using network pharmacology and molecular docking technology.@*METHODS@#The TCMSP database was used for screening the traditional Chinese drugs containing active ingredients for treating MI, and the related targets of MI and the candidate drugs were obtained from Genecards, OMIM, PharmGkb and PharmMapper databases. The common target network of the drug targets and disease targets was established using Venny2.1.0 software. GO and KEGG signal pathway enrichment analysis of the common targets was performed, and the protein-protein interaction (PPI) network was constructed for the targets. The targets in the PPI network were analyzed to identify the key targets, for which GO and KEGG pathway enrichment analyses were performed. Molecular docking was performed for the candidate ingredients and the key targets, and a total score ≥6 was used as the criteria for screening the therapeutic ingredients and their docking binding with key targets was verified. A human umbilical vein endothelial cell (HUVEC) model of oxygen-glucose deprivation (OGD) was used to validate the candidate ingredients and the key therapeutic targets for MI by Western blotting.@*RESULTS@#Our analysis identified Salvia miltiorrhiza and Dalbergiae odoriferae as the candidate drugs rich in active ingredients for treatment of MI. These ingredients involved 16 key therapeutic targets for MI, which participated in such biological processes as inflammatory response, angiogenesis, energy metabolism and oxidative stress and the pathways including HIF-1, VEGF, and TNF pathways. Sclareol and PTGS2 in Salvia miltiorrhiza and formononetin and KDR in Dalbergiae odoriferae all had high docking total scores. Western blotting showed that at medium and high doses, sclareol significantly inhibited PTGS2 expression and formononetin promoted KDR expressions in the cell models in a dose-dependent manner (P < 0.05).@*CONCLUSION@#Both Salvia miltiorrhiza and Dalbergiae odoriferae have good therapeutic effects on MI. Sclareol in Salvia miltiorrhiza and formononetin in Dalbergiae odoriferae regulate the expressions of KDR and PTGS2, respectively, to modulate the inflammatory response, angiogenesis, oxidative stress and energy metabolism and thus produce myocardial protective effects.

Efficacy of Pinggan Yuyin Qingre Recipe for Treatment of Hyperevaporative Dry Eye Disease Caused by Meibomian Gland Dysfunction / 中国实验方剂学杂志

Objective:To observe the therapeutical effect and the safety of Pinggan Yuyin Qingre recipe on the hyperevaporative dry eye disease （Yin deficiency and Yang hyperactivity type） caused by the meibomian gland dysfunction（MGD）. Method:The 120 Consecutive outpatients who met the criteria were included in the trial and divided into three layers （mild， moderate and severe） according to the meibomian gland function classification （grade 1-3）. The patients in each layer were randomly assigned to the experiment group and the control group at a ratio of 1∶1. Both groups were treated with sodium hyaluronate eye drops， 1 drop/eye/time， 3 times a day. In the experiment group， Pinggan Yuyin Qingre recipe was additionally prescribed two times a day. The treatment course was 8 weeks in both groups. All patients were evaluated at the beginning and end of the study mainly for noninvasive tear breakup time （NITBUT），corneal lesions score，meibomian gland exclusion score，meibomian gland structure，eye symptom score，the ocular surface disease index（OSDI） score，and the traditional Chinese medicine（TCM） syndrome scores at both overall and layered levels. Result:A total of 116 cases completed the study，with 1 drop-out case and 3 eliminated cases. Both before and after treatment，NITBUT，the corneal lesions score，the symptom score，and the OSDI score in the experiment group were significantly superior to the control group， but there was no significant difference in meibomian gland exclusion score between two groups，only with a superior tendency in experiment group. There were significant differences in the scores of the related TCM syndrome scores between two groups after treatment. There were no adverse reactions， no abnormal changes in electro cardiogram （ECG） or liver and kidney functions in all patients. Conclusion:Pinggan Yuyin Qingre recipe can effectively improve the hyperevaporative dry eye disease caused by meibomian gland dysfunction， the tear film stability，eye dryness， burning，itching，foreign body sensation and TCM symptoms of patients with dry eye syndrome of Yin deficiency and Yang hyperactivity. The improvement effect is more obvious in moderate and severe patients. It is an effective，safe，and well-tolerated treatment for the hyperevaporative dry eye.

Geriatric nutritional risk index predicts all-cause mortality in patients with heart failure: A systematic review and meta-analysis

OBJECTIVES: Geriatric nutritional risk index (GNRI) might predict the all-cause mortality in patients with heart failure (HF). We performed a meta-analysis to evaluate the correlation between GNRI and all-cause mortality in patients with HF. METHODS: We searched the PubMed, Medline, Cochrane Library, and Embase databases for clinical trials investigating the association between GNRI and all-cause mortality in patients with HF, having the primary endpoint as all-cause mortality. RESULTS: In total, nine studies involving 7,659 subjects were included in the systematic review and meta-analysis. The results indicated that major risk and moderate risk GNRI (GNRI<92) was associated with an increased risk of all-cause mortality in elderly patients with HF (hazard ratios [HR] 1.59, 95% confidence intervals [CI] 1.37-1.85). Low risk GNRI (GNRI<98) group predicted all-cause mortality in elderly HF patients (HR 1.56, 95%CI 1.12-2.18) when compared with the high GNRI value group. A subgroup analysis indicated that the relationship between GNRI and HF might differ based on the subtype of heart failure. CONCLUSIONS: GNRI is a simple and well-established nutritional assessment tool to predict all-cause mortality in patients with HF.

Wnt5a modulates vincristine resistance through PI3K/Akt/GSK3β signaling pathway in human ovarian carcinoma SKOV3/VCR cells / 生理学报

The aim of this study was to investigate the effect of Wnt5a on the vincristine (VCR) resistance in human ovarian carcinoma SKOV3 cells and its possible mechanism. The drug-resistant SKOV3/VCR cells were established by stepwise exposure to VCR, and then the SKOV3/VCR cells were stably transfected with specific shRNA interference plasmid vector targeting for Wnt5a. The mRNA expression level of Wnt5a was measured by RT-PCR. CCK-8 assay was used to detect the cell viability of SKOV3/VCR cells. The apoptosis was analyzed by flow cytometry. The protein expression levels of Wnt5a, MDR1, Survivin, β-catenin, Akt, p-Akt(S473), GSK3β and p-GSK3β(Ser9) were detected by Western blot. The result showed that SKOV3/VCR cells had significantly higher protein expression levels of Wnt5a, MDR1, Survivin and β-catenin, phosphorylation levels of Akt and GSK3β, and mRNA expression level of Wnt5a, compared with SKOV3 cells (P < 0.05). WNT5A gene silencing significantly increased the sensitivity of SKOV3/VCR cells to VCR, the IC of VCR being decreased from 38.412 to 9.283 mg/L (P < 0.05), synergistically enhanced VCR-induced apoptosis of SKOV3/VCR cells (P < 0.05), down-regulated the protein expression levels of MDR1, β-catenin and Survivin (P < 0.05), and inhibited phosphorylation of Akt and GSK3β (P < 0.05). Meanwhile, LY294002 (PI3K inhibitor) decreased the protein expression levels of MDR1, β-catenin and Survivin, as well as the phosphorylation levels of Akt and GSK3β in SKOV3/VCR cells (P < 0.05). These results suggest that WNT5A gene silencing reverses VCR resistance in SKOV3/VCR cells possibly through blocking the PI3K/Akt/GSK3β/β-catenin signaling pathway, and thus down-regulating the protein expression levels of MDR1 and Survivin.

Therapeutic drug monitoring of teicoplanin:an overview / 国际药学研究杂志

Teicoplanin is a new glycopeptide antibiotic marketed after vancomycin for the treatment of Staphylo- coccus aureus(SAU)infection. Previous studies have shown that teicoplanin is safer than vancomycin,especially in the nephrotoxicity,so the routine serum concentration monitoring was not performed in the clinical application of teico- planin. In recent years,it has been found that the individual differences frequently appeared in the clinical application of teicoplanin,and thus it has been suggested that the serum concentration monitoring should be carried out in its clinical application. However,the domestic studies on the serum teicoplanin concentration monitoring are rarely conducted,and its clinical application experience is insufficient in China. This paper reviews the therapeutic drug monitoring of teico- planin,in terms of the pharmacokinetic characteristics of teicoplanin,the correlation between the blood concentration with the efficacy and adverse reactions,and the factors influencing the blood concentration of teicoplanin,so as to pro- vide a reference for the therapeutic drug monitoring and the rational clinical application of teicoplanin.

Effect of proton pump inhibitors on tacrolimus blood concentration in organ transplant recipients / 国际药学研究杂志

Tacrolimus,a macrolide immunosuppressive agent,has been used as a first-line drug for the inhibi- tion of rejection after organ transplantation. In general, the organ-transplanted patients need to administer proton pump in- hibitors to prevent gastrointestinal syndrome when tacrolimus is used,and a high proportion of patients use the two drug combination. However,the combined use of tacrolimus with the proton pump inhibitor often gives rise to the fluctuation in the tacrolimus blood concentration. This fluctuation has been suggested to be likely related to the competition of the CYP3A4 metabolic enzyme between the two drugs. In this paper,the interaction between tacrolimus and different kinds of proton pump inhibitors is reviewed in order to provide reference for their clinical application.

Intestinal absorption of phenolic acids in Rhus chinensis extracts by in situ single-pass perfusion model in rats / 中国中药杂志

The intestinal absorption properties of four main effective components(gallic acid, ocinolglucoside, ethyl gallate and penta-O-galloyl-β-D-glucose) in Rhus chinensis extracts were investigated by in situ single-pass intestinal perfusion model in rats. The liquid accumulation of perfusion was corrected by gravimetry. The HPLC method was established to determine the concentration of the four effective components in the intestinal perfusion. It showed significant differences(Pethyl gallate>gallic acid>ocinolglucoside, with significant differences between them(P<0.05). In conclusion, gallic acid, orpheolglucoside, ethyl gallate and pentacyl-glucose could be absorbed in the whole intestine. Their absorption rate and permeation ability were related to the intestinal section and the perfusate concentration. These results indicated potential active transport or facilitated diffusion in the intestinal transport process of the four effective components.

Changes of cardiac function, RAGE expression and calcium dysregula-tion in type 2 diabetic rats / 中国病理生理杂志

AIM:To investigate the changes of cardiac structure and function in rats with type 2 diabetic melli-tus(T2DM),and to explore the mechanisms underlying diabetic cardiomyopathy.METHODS:The cardiac structure and function were measured by echocardiography in Zucker diabetic fatty(ZDF)rats and their control Zucker lean(ZL)rats. The size of the cardiomyocytes was determined by wheat germ agglutinin staining.The protein expression of atrial natriuretic peptide(ANP),β-myosin heavy chain(β-MHC), receptor for advanced glycation end products(RAGE), L-type cal-cium channel α1C subunit(CaV1.2)and Orai1 was assessed by Western blot.RESULTS:Compared with the ZL control rats,the thickness of left ventricular wall,ejection fraction(EF),fractional shortening(FS)and the sizes of cardiomyo-cytes were significantly increased,and diastolic function was decreased in the ZDF rats(P<0.05).The protein expression of β-MHC, ANP, RAGE and Orai1 was increased, while the expression of Ca V1.2 was decreased in ZDF rats(P <0.05).CONCLUSION:T2DM rats show the prominent features including cardiomyocyte hypertrophy,ventricular hyper-trophy and compensatory enhancement of cardiac function, and the Ca2+handling and increase in RAGE expression may play important roles in the processes.

Comparison on the visual quality after different multifocal lens implantation in cataract patients / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To compare the visual quality after different multifocal lens (MIOL) implantation in cataract patients. ·METHODS: Totally 78 cases (78 eyes) of cataract patients who receiving phacoemulsification and implantation of different MIOL were enrolled from February 2016 to June 2017 in our hospital. According to the different type of implanted MIOL, the 78 cases (78 eyes) were divided Group A,B and C,each group was 26 cases (26 eyes). Patients in the Group A were implanted regional refraction MIOL SBL-3; patients in the Group B implanted step progressive diffraction MIOL SN6AD1;patients in the Group C implanted all - optical plane diffraction MIOL Tecnis ZMB00. The visual acuity, contrast sensitivity,defocus testing,contrast visual acuity and satisfaction of visual quality were compared in 3 groups at postoperative 3mo. · RESULTS: There was no statistically significant difference in postoperative adverse reactions between the three groups (P>0.05). There was statistical difference in uncorrected intermediate visual acuity, uncorrected near visual acuity, distance - corrected intermediate visual acuity and distance- corrected near visual acuity in 3 groups (P < 0. 05), and those in the Group C were significantly worse than those of Group A and B (P<0.05). There was statistical difference in contrast sensitivity at four spatial frequencies (3,6,12,18c/d) in light and light glare and three spatial frequencies (3, 6, 12c/d) in dark and dark glare in 3 groups (P<0.05), and those in the Group A were significantly better than those of Group B and C (P<0.05). According to the defocus testing of 3 groups,the visual acuity at -1.5D,-2.0D and-2. 5D in Group A and B was significantly higher than Group C (P<0. 05). There was statistical difference in contrast visual acuity at 20% and 9% of contrast ratio in 3 groups (P<0.05),and those in Group A were significantly better than Group B and C(P<0.05). There was statistical difference in visual quality satisfaction in 3 groups (P<0.05), and that in the Group A was significantly better than that of Group B and C (P<0.05). ·CONCLUSION:The region refraction MIOL SBL-3 not only could provide better distant, intermediate and near visual acuity, but also could provide better contrast sensitivity and contrast visual acuity, thereby greatly increase visual quality satisfaction.

Clinical efficacy of segmented bifocal intraocular lens SBL-3 / 国际眼科杂志(Guoji Yanke Zazhi)

·AMI:To evaluate the clinical efficacy of the segmented bifocal intraocular lens (MIOL) SBL-3. ·METHODS:Totally 26 cases (26 eyes) of age-related cataract who received phacoemulsification and implantation of MIOL SBL-3 were enrolled from February 2016 to June 2017 in our hospital as the SBL-3 group. And 28 cases (28 eyes) of age-related cataract who received phacoemulsification and implantation of single focus intraocular lens intraocular lens TecnisZA9003 were enrolled as control group. At postoperative 3mo, the uncorrected visual acuity, corrected visual acuity, contrast sensitivity and patient satisfaction were compared between two groups. ·RESULTS: At preoperative, there was no statistical difference in uncorrected distance, intermediate and near visual acuity between two groups (P > 0. 05). At postoperatively 3mo, the uncorrected distance, intermediate and near visual acuity in patients of both groups were significantly improved (P < 0. 05). At postoperative 3mo,the uncorrected intermediate and near visual acuity, distance-corrected intermediate and near visual acuity, contrast sensitivity at different spatial frequencies (3, 6, 12, 18c/d) and patient satisfaction in SBL- 3 group were significantly better than those of control group (P<0.05). ·CONCLUSION:The MIOL SBL-3 not only could provide preferable distance visual acuity, but also could provide better intermediate visual acuity, near visual acuity and contrast sensitivity,and greatly increase the visual quality and satisfaction at postoperative in cataract patients.

Efficacy of Benefiting Qi for Warming Yang and Activating Blood Circulation with Western Medicine for Inducing Diuresis in the Patients with Chronic Heart Failure and its Effect on the Expression of Circulating miRNAs / 中国药师

Objective:To observe the efficacy of benefiting Qi for warming Yang and activating blood circulation for inducing diu-resis method in the treatment of patients with chronic heart failure( CHF) and its effect on the expression of circulating miRNAs ( miR-423-5p, miR-210-3p). Methods:Totally 80 CHF patients were randomly divided into two groups,the control group with 40 patients was treated with the conventional anti-heart failure therapy, and the treatment group with 40 patients was treated with benefiting Qi for warming Yang and activating blood circulation for inducing diuresis decoction on the basis of the control group, and the treatment course was 2 weeks. The clinical efficacy and syndrome integral of traditional Chinese medicine ( TCM) were evaluated. Left ventricular ejec-tion fraction ( LVEF) and left ventricular end diastolic diameter( LVEDD) were measured by echocardiography;the plasma expression levels of circulating miRNAs(miR-423-5p, miR-210-3p) were measured by real-time PCR in the two groups before and after the treat-ment. The adverse drug reactions were observed as well. Results:The total clinical effective rate of the treatment group was significant-ly higher than that of the control group (87. 50% vs 65. 00%, P <0. 05); the syndrome integral of TCM, indices of LVEF and LVEDD and the expression of circulating miRNAs were improved in both groups(P<0. 05);the total clinical effective rate, syndrome integral of TCM, indices of LVEF and LVEDD and the expression of circulating miR-423-5p of the treatment group were better than those of the control group(P<0. 05); there was no significant difference in adverse drug reactions between the groups (P>0. 05). Conclusion:The benefiting Qi for warming Yang and activating blood circulation for inducing diuresis method can improve the clinical effects in the treatment of CHF, and improve the expression of circulating miRNAs.

Establishment of Congenital Heart Disease Transposition of Great Arteries in Experimental Mice Model / 中国循环杂志

Objective: To establish a mice model of congenital heart disease transposition of great arteries in order to provide a research reference for the occurrence and development of transposition of great arteries. Methods: A total of 20 pregnant ICR mice at 8-10 weeks of age were divided into 2 groups: Control group, the mice received a single dose of DMSO 70 mg/kg at 8.5 days of gestation,n=5 and Experiment group, the mice received a single dose of all-trans retinoic acid 70 mg/kg at 8.5 days of gestation,n=15. All animals were treated for 18 days and then the embryos were taken to observe cardiac morphology under stereomicroscope. Results: Compared with Control group, Experiment group had obviously increased occurrence rates of premature delivery, abortion and embryo absorption, and 61.2% phenotype for transposition of great arteries; meanwhile, combining with non-heart defect phenotypeas exophthalmos and spinal malformation. Conclusion: All-trans retinoic acid may induce transposition of great arteries in mice embryos, which is a feasible animal model in experimental research.

Study on HPLC fingerprint and chemical constituent difference of different species of Aurantii Fructus Immaturus / 中国中药杂志

This study is to establish an HPLC fingerprint by HPLC-DAD method and simultaneous quantitative analysis of 17 components of 18 batches of Citrus aurantium and 10 batches of C. sinensis. The separation was performed on an Agilent Poroshell 120 SB-C₁₈ (4.6 mm×100 mm,2.7 μm) column with the gradient elution of methanol-0.1% formic acid water, the flow was 0.6 mL•min⁻¹. The detection wavelength was set at 318 nm. The column temperature was maintained at 30 ℃. The data calculation was performed with similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine (Version 2004A) together with SIMCA-P 13.0 software to clarify the differential marker between these two different species of Aurantii Fructus Immaturus. This method has good precision stability and repeatability that could provide basis for quality control and evaluation of Aurantii Fructus Immaturus.

Parkinson's Disease with Fatigue: Clinical Characteristics and Potential Mechanisms Relevant to α-Synuclein Oligomer

BACKGROUND AND PURPOSE: The aim of this study was to identify the clinical characteristics and potential mechanisms relevant to pathological proteins in Parkinson's disease (PD) patients who experience fatigue. METHODS: PD patients (n=102) were evaluated using a fatigue severity scale and scales for motor and nonmotor symptoms. The levels of three pathological proteins-α-synuclein oligomer, β-amyloid (Aβ)(1-42), and tau-were measured in 102 cerebrospinal fluid (CSF) samples from these PD patients. Linear regression analyses were performed between fatigue score and the CSF levels of the above-listed pathological proteins in PD patients. RESULTS: The frequency of fatigue in the PD patients was 62.75%. The fatigue group had worse motor symptoms and anxiety, depression, and autonomic dysfunction. The CSF level of α-synuclein oligomer was higher and that of Aβ1-42 was lower in the fatigue group than in the non-fatigue group. In multiple linear regression analyses, fatigue severity was significantly and positively correlated with the α-synuclein oligomer level in the CSF of PD patients, after adjusting for confounders. CONCLUSIONS: PD patients experience a high frequency of fatigue. PD patients with fatigue have worse motor and part nonmotor symptoms. Fatigue in PD patients is associated with an increased α-synuclein oligomer level in the CSF.