Effects of alcohol on the composition and metabolism of the intestinal microbiota among people with HIV: a cross-sectional study.

OBJECTIVES: Alcohol consumption is not uncommon among people with HIV (PWH) and may exacerbate HIV-induced intestinal damage, and further lead to dysbiosis and increased intestinal permeability. This study aimed to determine the changes in the faecal microbiota and its association with alcohol consumption in HIV-infected patients. METHODS: A cross-sectional survey was conducted between November 2021 and May 2022, and 93 participants were recruited. To investigate the alterations of alcohol misuse on fecal microbiology in HIV-infected individuals, we performed 16s rDNA gene sequencing on fecal samples from the low to moderate drinking (n=21) and non-drinking (n=72) groups. RESULTS: Comparison between groups using alpha and beta diversity showed that the diversity of stool microbiota in the low to moderate drinkinge group did not differ from that of the non-drinking group (all P>0.05). The Linear discriminant Analysis effect size (LEfSe) algorithm was to determine the bacterial taxa associated with alcohol consumption, and the results showed altered fecal bacterial composition in HIV-infected patients who consumed alcohol, with Coprobacillus, Pseudobutyrivibrio and Peptostreptococcaceae enriched, and Pasteurellaceae and Xanthomonadaceae were depleted. In addition, by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional microbiome features were also found to be altered in the low to moderate drinking group, showing a reduction in metabolic pathways (P=0.036) and cardiovascular disease pathway (P=0.006). CONCLUSION: Low to moderate drinking will change the composition, metabolism and cardiovascular disease pathway of the gut microbiota of HIV-infected patients.

Metabolomic profiles, polygenic risk scores and risk of rheumatoid arthritis: a population-based cohort study in the UK Biobank.

OBJECTIVE: To investigate the relationship between metabolomic profiles, genome-wide polygenic risk scores (PRSs) and risk of rheumatoid arthritis (RA). METHODS: 143 nuclear magnetic resonance-based plasma metabolic biomarkers were measured among 93 800 participants in the UK Biobank. The Cox regression model was used to assess the associations between these metabolic biomarkers and RA risk, and genetic correlation and Mendelian randomisation analyses were performed to reveal their causal relationships. Subsequently, a metabolic risk score (MRS) comprised of the weighted sum of 17 clinically validated metabolic markers was constructed. A PRS was derived by assigning weights to genetic variants that exhibited significant associations with RA at a genome-wide level. RESULTS: A total of 620 incident RA cases were recorded during a median follow-up time of 8.2 years. We determined that 30 metabolic biomarkers were potentially associated with RA, while no further significant causal associations were found. Individuals in the top decile of MRS had an increased risk of RA (HR 3.52, 95% CI: 2.80 to 4.43) compared with those below the median of MRS. Further, significant gradient associations between MRS and RA risk were observed across genetic risk strata. Specifically, compared with the low genetic risk and favourable MRS group, the risk of incident RA in the high genetic risk and unfavourable MRS group has almost elevated by fivefold (HR 6.10, 95% CI: 4.06 to 9.14). CONCLUSION: Our findings suggested the metabolic profiles comprising multiple metabolic biomarkers contribute to capturing an elevated risk of RA, and the integration of genome-wide PRSs further improved risk stratification.

Dihydroartemisinin attenuates ischemia/reperfusion-induced renal tubular senescence by activating autophagy / 中国天然药物

Acute kidney injury (AKI) is an important factor for the occurrence and development of CKD. The protective effect of dihydroartemisinin on AKI and and reported mechanism have not been reported. In this study, we used two animal models including ischemia-reperfusion and UUO, as well as a high-glucose-stimulated HK-2 cell model, to evaluate the protective effect of dihydroartemisinin on premature senescence of renal tubular epithelial cells in vitro and in vivo. We demonstrated that dihydroartemisinin improved renal aging and renal injury by activating autophagy. In addition, we found that co-treatment with chloroquine, an autophagy inhibitor, abolished the anti-renal aging effect of dihydroartemisinin in vitro. These findings suggested that activation of autophagy/elimination of senescent cell might be a useful strategy to prevent AKI/UUO induced renal tubular senescence and fibrosis.

Exploration and practice of clinical engineer training mode / 中华医学教育探索杂志

Objective:To explore the training mode of continuing education for clinical engineers, and provide reference for the training of clinical engineers.Methods:A total of 31 clinical engineers were selected as the two-stage training mode combined with short-term centralized intensive basic training and standardized post professional training. Comparative analysis of assessment scores before and after training was performed, and the satisfaction of comprehensive effect and post competency improvement after training was evaluated. SPSS 19.0 was used for t-test. Results:The assessment scores after training (85.06±7.31) were significantly higher than those before (69.55±6.74) training ( P = 0.001). The comprehensive training effect of clinical engineers and the satisfaction rate of post competency improvement reached a high level, which were 70.97% (22/31) and 83.87% (26/31), respectively. Conclusion:The two-stage training mode combined with short-term centralized basic intensive training and standardized post professional training can not only effectively improve the theoretical knowledge level, practical ability and post competency of clinical engineers, but also shorten the centralized training time, which is conducive to solving the practical problems that affect the continuing education training program due to the lack of human resources of clinical engineers.

Interleukin-6 Elevation Is a Key Pathogenic Factor Underlying COVID-19-Associated Heart Rate-Corrected QT Interval Prolongation.

Background: Heart rate-corrected QT interval (QTc) prolongation is prevalent in patients with severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. Recent evidence suggests that the exaggerated host immune-inflammatory response characterizing the disease, specifically interleukin-6 (IL-6) increase, may have an important role, possibly via direct effects on cardiac electrophysiology. The aim of this study was to dissect the short-term discrete impact of IL-6 elevation on QTc in patients with severe COVID-19 infection and explore the underlying mechanisms. Methods: We investigated the following mechanisms: (1) the QTc duration in patients with COVID-19 during the active phase and recovery, and its association with C-reactive protein (CRP) and IL-6 levels; (2) the acute impact of IL-6 administration on QTc in an in vivo guinea pig model; and (3) the electrophysiological effects of IL-6 on ventricular myocytes in vitro. Results: In patients with active severe COVID-19 and elevated IL-6 levels, regardless of acute myocardial injury/strain and concomitant QT-prolonging risk factors, QTc was significantly prolonged and rapidly normalized in correlation with IL-6 decrease. The direct administration of IL-6 in an in vivo guinea pig model acutely prolongs QTc duration. Moreover, ventricular myocytes incubated in vitro with IL-6 show evident prolongation in the action potential, along with significant inhibition in the rapid delayed rectifier potassium current (IKr). Conclusion: For the first time, we demonstrated that in severe COVID-19, systemic inflammatory activation can per se promote QTc prolongation via IL-6 elevation, leading to ventricular electric remodeling. Despite being transitory, such modifications may significantly contribute to arrhythmic events and associated poor outcomes in COVID-19. These findings provide a further rationale for current anti-inflammatory treatments for COVID-19, including IL-6-targeted therapies.

Waste tobacco leaves derived carbon dots for tetracycline detection: Improving quantitative accuracy with the aid of chemometric model.

The recycling and reutilization of biomass wastes are significant for environmental protection and sustainable development. Recently, there have many studies on utilizing biomass wastes to produce carbon dots. Whereas, the spectrum shift effect that occurs in the quantitative application of carbon dots as fluorescent probes limits the accuracy of the quantitative analysis. In this work, waste tobacco leaves were used as the carbon source for synthesizing a novel carbon dots (CDs(WTL)) through a facile hydrothermal method. The CDs(WTL) possess a series of excellent properties, including good water solubility, well stability, and high fluorescence quantum yield. The fluorescent intensity of the CDs(WTL) can be quenched by tetracycline (TC) obviously, but there is a spectrum shift. In order to use the CDs(WTL) as fluorescent probes to quantify TC with higher accuracy, a quantification fluorescence model (QFM) was introduced to overcome this spectrum shift effect that often occurs. The coefficient of determination (R2) of traditional quantification model (TQ), partial least squares (PLS), and QFM are 0.9672, 0.9834, and 0.9991, respectively; the average relative predictive error (ARPE) of TQ, PLS, and QFM are 8.8%, 4.5%, and 3.9% for the spiked water samples, and 21.9%, 22.0%, and 2.9% for spiked tablet samples, respectively. The obtained results suggest that QFM is more accurate than PLS and TQ for the TC detection. By utilizing QFM, the spike recoveries (mean ± standard deviation) in three kinds of real tablet samples produced by different manufacturers are 98.9 ± 3.6%, 102.5 ± 6.2%, and 98.5 ± 2.7%, respectively; the spike recovery in river water samples is 99.4 ± 5.0%. In addition, high performance liquid chromatography (HPLC) was used as a reference method, the F and t tests suggest that there are no significant differences on the precision and accuracy between QFM and HPLC methods.

IL-6 exacerbates potential arrhythmia of Chan Su intravenous injection / 中国药理学通报

Aim To explore the arrhythmic risk of Chan Su intravenous injection(CS)and its underlying mechanismin in the absent or presence of IL-6.Methods The recording techniques of guinea pig in vivo ECG, the action potential, L-type Ca2+ and Na+ currents from left ventricular myocytes were used to analyze heart rate(HR), P-R, QRS and QTc intervals and the underlying mechanism.Results① CS at one time CRD(clinically relevant dose)insignificantly changed the guinea pig in vivo ECG.However, the IL-6(18.4 μg·kg-1)only and the combinational use of IL-6(18.4 μg·kg-1)plus CS(one time CRD)remarkably prolonged the P-R and QTc intervals.② The CS at one time CRC(clinically relevant concentration)had no significant change in the action potential duration at 90% repolarization level(APD90).The IL-6(20 μg·L-1)only and the combination of CS at one time CRC plus IL-6(20 μg·L-1)significantly prolonged APD90.③ Moreover, the IL-6(20 μg·L-1)combined with CS at one time CRC significantly inhibited the L-type Ca2+ current. CS at one, five, ten time CRC, IL-6(20 μg·L-1)alone and IL-6(20 μg·L-1)combined with CS had no significant effects on Na+current.Conclusions CS intravenous injection has low risk of arrhythmia in the clinical settings.However, in presence of high titer of IL-6 characterized by inflammation, CS may induce the atrioventricular conduction block due to the blockade effect on Ca2+ current by both of CS and IL-6.

Comparative analysis of pathological structure between acute closed and open Achilles tendon rupture / 中国骨伤

OBJECTIVE@#To investigate the morphological, histological and ultrastructural changes of acute closed rupture of Achilles tendon, in order to clarify the pathological basis of the injury and to explore the significance.@*METHODS@#From January 2015 to January 2019, 35 patients with acute Achilles tendon rupture who underwent the minimally invasive Achilles tendon suture technique were retrospectively analyzed. Among these patients, 12 cases in acute open Achilles tendon rupture group included 10 males and 2 females, with an average age of (35.1±9.7) years old ranging from 19 to 50, and the time from injury to operation was 2 to 8 hours with an average of(5.6±1.8);23 cases in acute closed Achilles tendon rupture group included 21 males and 2 females, with an average age of (35.5±6.6) years old ranging from 18 to 50, and the time from injury to operation was 3 to 15 hours with an average of (7.5±3.1). The gross appearance and imaging findings of the broken end of Achilles tendon tissue in the two groups were compared by naked eye observation and foot and ankle MRI at 4 to 6 hours before operation. HE staining, scanning and fluoroscopic electron microscopy, immunohistochemistry(Sirius red staining) were performed on the intraoperative Achilles tendon tissue specimens at 1 to 2 days after operation, the collagen fiber degeneration and local fat infiltration, collagen fiber shape, cell morphology and function, and the distribution of typeⅠand type Ⅲ collagen fibers in Achilles tendon were compared between the two groups.@*RESULTS@#Compared with the acute open Achilles tendon rupture group, the acute closed Achilles tendon rupture group had poor elasticity, hard texture, moderate edema, irregular shape of Achilles tendon broken end, horsetail shape, and more calcification around the broken end. HE staining results:the collagen fibers in the Achilles tendon of the acute open Achilles tendon rupture group were arranged irregularly, with hyaline degeneration and fat infiltration;The results of electron microscopy showed that collagen arranged disorderly and fibroblasts atrophied in the acute closed Achilles tendon rupture group. Immunohistochemical(Sirius staining) results:the proportion of collagenⅠin the acute open Achilles tendon rupture group and the acute closed Achilles tendon rupture group was(91.12±4.34)% and(54.71±17.78)% respectively, and the proportion of collagen Ⅲ was (8.88±4.34)% and (45.29±17.78)% respectively. The content of collagenⅠin the acute closed Achilles tendon rupture group was lower than that in the acute open Achilles tendon rupture group, and the content of collagen Ⅲ in the acute closed Achilles tendon rupture group was higher than that in the acute open Achilles tendon rupture group(P<0.05).@*CONCLUSION@#The morphology, histology and ultrastructure of the acute closed ruptured Achilles tendon are significantly altered compared with the normal Achilles tendon. The original fine and orderly spatial structure cannot be maintained, part of collagen Ⅰ is replaced by collagen Ⅲ, and the toughness and strength of the tendon tissue decreased, which may be the feature of degeneration of the Achilles tendon and an important pathological basis for closed Achilles tendon rupture.

Bay 60-7550, a PDE2 inhibitor, exerts positive inotropic effect of rat heart by increasing PKA-mediated phosphorylation of phospholamban.

This study investigated the hemodynamic effect of Bay 60-7550, a phosphodiesterase type 2 (PDE2) inhibitor, in healthy rat hearts both in vivo and ex vivo and its underlying mechanisms. In vivo rat left ventricular pressure-volume loop, Langendorff isolated rat heart, Ca2+ transient of left ventricular myocyte and Western blot experiments were used in this study. The results demonstrated that Bay 60-7550 (1.5 mg/kg, i. p.) increased the in vivo rat heart contractility by enhancing stroke work, cardiac output, stroke volume, end-diastolic volume, heart rate, and ejection fraction. The simultaneous aortic pressure recording indicated that the systolic blood pressure was increased and diastolic blood pressure was decreased by Bay 60-7550. Also, the arterial elastance which is proportional to the peripheral vessel resistance was significantly decreased. Bay 60-7550 (0.001, 0.01, 0.1, 1 µmol/l) also enhanced the left ventricular development pressure in non-paced and paced modes with a decrease of heart rate in non-paced model. Bay 60-7550 (1 µmol/l) increased SERCA2a activity and SR Ca2+ content and reduced SR Ca2+ leak rate. Furthermore, Bay 60-7550 (0.1 µmol/l) increased the phosphorylation of phospholamban at 16-serine without significantly changing the phosphorylation levels of phospholamban at 17-threonine and RyR2. Bay 60-7550 increased the rat heart contractility and reduced peripheral arterial resistance may be mediated by increasing the phosphorylation of phospholamban and dilating peripheral vessels. PDE2 inhibitors which result in a positive inotropic effect and a decrease in peripheral resistance might serve as a target for developing agents for the treatment of heart failure in clinical settings.

The positive inotropic effect of phosphodiesterase type 8 inhibitor of PF-04957325 in rats and its underlying mechanism / 中国药理学通报

Aim To investigate the inotropic effect of PF-04957325, a phosphodiesterase type 8 inhibitor, in normal rats and its underlying molecular mechanism. Methods The techniques of in vivo rat left ventricular pressure-volume loop (P-V loop) and isolated perfusion rat heart were used to analyze the hemodynamics and positive inotropic effect of rat hearts. The Ca transient induced by field stimulation was used to analyze the hemodynamics of sarcoplasmic reticulum (SR) Ca + uptaking. Western blot was used to analyze the phosphorylation levels of SR phospolamban (PLB) and ryanodine receptor type 2 (RyR2). Results The P-V loop experiment indicated that PF-04957325 (0.5 mg · kg

Rapid Qualitative and Quantitative Analysis of Caffeine and Sodium Benzoate in Annaca by Infrared Spectroscopy / 法医学杂志

Objective To establish an infrared spectroscopic method for the rapid qualitative and quantitative analysis of caffeine and sodium benzoate in Annaka samples. Methods Qualitative and quantitative modeling samples were prepared by mixing high-purity caffeine and sodium benzoate. The characteristic absorption peaks of caffeine and sodium benzoate in Annaka samples were determined by analyzing the infrared spectra of the mixed samples. The quantitative model of infrared spectra was established by partial least squares （PLS）. Results By analyzing the infrared spectra of 17 mixed samples of caffeine and sodium benzoate （the purity of caffeine ranges from 10% to 80%）, the characteristic absorption peaks for caffeine were determined to be 1 698, 1 650, 1 237, 972, 743, and 609 cm-1. The characteristic absorption peaks for sodium benzoate were 1 596, 1 548, 1 406, 845, 708 and 679 cm-1. When the detection of all characteristic absorption peaks was the positive identification criteria, the positive detection rate of caffeine and sodium benzoate in 48 seized Annaka samples was 100%. The linear range of PLS quantitative model for caffeine was 10%-80%, the coefficient of determination （ R2） was 99.9%, the root mean square error of cross validation （RMSECV） was 0.68%, and the root mean square error of prediction （RMSEP） was 0.91%; the linear range of PLS quantitative model for sodium benzoate was 20%-90%, the R2 was 99.9%, the RMSECV was 0.91% and the RMSEP was 1.11%. The results of paired sample t test showed that the differences between the results of high performance liquid chromatography method and infrared spectroscopy method had no statistical significance. The established infrared quantitative method was used to analyze 48 seized Annaka samples, the purity of caffeine was 27.6%-63.1%, and that of sodium benzoate was 36.9%-72.3%. Conclusion The rapid qualitative and quantitative analysis of caffeine and sodium benzoate in Annaka samples by infrared spectroscopy method could improve identification efficiency and reduce determination cost.

Sirtuin (Sirt) 3 Overexpression Prevents Retinopathy in Streptozotocin-Induced Diabetic Rats.

BACKGROUND Sirtuin (Sirt) 3 could promote autophagy by downregulating the expression of genes related to neovascularization in retinal endothelial cells. In this study, we aimed to investigate the effect of Sirt3 overexpression on retinopathy in streptozotocin (STZ)-induced diabetic rats, and to assess its mechanisms. MATERIAL AND METHODS Ntraperitoneal injection of STZ in rats was used to produce a diabetic model. The study rats were divided into 4 groups (n=6 for each group): a control group; a model group; a model+scrambled adenovirus group; and a model+Sirt3 overexpression group. Hematoxylin and eosin (H&E) staining determined the pathological changes of retina tissues. Immunohistochemistry, fluorescence quantitative polymerase chain reaction, and western blotting were used to detect the expression of Sirt3, vascular endothelial growth factor (VEGF), and microtubule-associated protein 1A/1B-light chain 3 (LC3). RESULTS In the model group, the inner limiting membrane was swollen, uneven and thickened, and the capillary endothelial cells occasionally protruded into the inner limiting membrane. These abnormalities were prevented by Sirt3 overexpression. Compared with the control group, the expression of Sirt3 at both mRNA and protein levels in the model group was significantly reduced, while the expression of VEGF was increased versus the control group (P.

Increased sarcoplasmic/endoplasmic reticulum calcium ATPase 2a activity underlies the mechanism of the positive inotropic effect of ivabradine.

NEW FINDINGS: What is the central question of this study? The therapeutic effect of ivabradine on patients with chronic heart failure and chronic stable angina pectoris is mediated through a reduction in heart rate: what are the haemodynamic characteristics and the mechanism of the inotropic effect? What is the main finding and its importance? Ivabradine has a positive inotropic effect and lowers the heart rate both in vivo and in vitro. These effects are likely mediated by ivabradine's significant increase of the fast component rate constant mediated by sarcoplasmic/endoplasmic reticulum calcium ATPase 2a and decrease of the slow component rate constant that is mediated by the Na+ /Ca2+ exchanger and sarcolemmal Ca2+ -ATPase during the Ca2+ transient decay phase. ABSTRACT: Ivabradine's therapeutic effect is mediated by a reduction of the heart rate; however, its haemodynamic characteristics and the mechanism of its inotropic effect are poorly understood. We aimed to investigate the positive inotropic effect of ivabradine and its underlying mechanism. The results demonstrated that ivabradine increased the positive inotropy of the rat heart in vivo by increasing the stroke work, cardiac output, stroke volume, end-diastolic volume, end-systolic pressure, ejection fraction, ±dP/dtmax , left ventricular end-systolic elastance and systolic blood pressure without altering the diastolic blood pressure and arterial elastance. This inotropic effect was observed in both non-paced and paced rat isolated heart. Ivabradine increased the Ca2+ transient amplitude and the reuptake rates of sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a), lowered the diastolic Ca2+ level and suppressed the combined extrusion rate of the Na+ /Ca2+ exchanger and the sarcolemmal Ca2+ -ATPase. In addition, ivabradine widened the action potential duration, hyperpolarized the resting membrane potential, increased sarcoplasmic reticulum Ca2+ content and reduced Ca2+ leak. Overall, ivabradine had a positive inotropic effect brought about by enhanced SERCA2a activity, which might be mediated by increased phospholamban phosphorylation. The positive inotropic effect along with the lowered heart rate underlies ivabradine's therapeutic effect in heart failure.

Epidemiological characteristics of patients with coronavirus disease 2019 in Chenzhou City / 上海预防医学

Objective To identify the epidemiological features of COVID-19 epidemic in Chenzhou City, Hunan province so as to provide scientific evidence for effective containment of the COVID-19 epidemic. Methods Descriptive epidemiological method was used to retrospectively characterize the confirmed COVID-19 cases and asymptomatic cases in Chenzhou City from January 23 through March 10, 2020. Results A total of 39 confirmed COVID-19 cases and 6 asymptomatic cases infection were documented in the city, with no death.We identified 8 clusters of COVID-19, which were all familial transmission.There was statistical difference between the sources of different types of epidemic (χ2=15.996, P < 0.001), in which all the local COVID-19 cases were the secondary cases in the clusters.As the epidemic expanded, the trend shifted from imported-case-centered to local-case-centered.The epidemic has covered 81.81% of the city area; in each area, the first COVID-19 cases were all imported. Conclusion The COVID-19 epidemic has been effectively controlled.At present, we focus on the quarantine in the entry and exit to prevent the imported epidemic.

Analysis of the clinical pathological characteristics and prognosis of primary IgA nephropathy with hypertension / 中华肾脏病杂志

Objective@#To investigate the clinic-pathological features and prognostic risk factors of IgA nephropathy (IgAN) with hypertension (HTN).@*Methods@#Primary IgAN patients diagnosed with biopsy from January 2016 to December 2017 were recruited. Patients were divided into IgAN with normal blood pressure (IgAN-NTN) group and IgAN with hypertension (IgAN-HTN) group based on the pressure value when performing the kidney biopsy. The clinical and pathological data were collected and compared between the two groups. Kaplan-Meier method was conducted for renal results, whereas the Cox regression model was exploited to analyze the prognostic factors in the progression of IgAN-HTN patients.@*Results@#The total number of enrolled patients was 275 cases, 170 (61.82%) of which had normal pressure and 105 individuals (38.18%) resulted in hypertension. The IgAN-HTN group in terms of male proportion, age, systolic pressure, diastolic pressure, serum urea nitrogen, serum creatinine, serum uric acid, 24 h urinary protein, triacylglycerol, complement C4 and so on were higher than those in the IgAN-NTN group (all P<0.05). The incidence of gross hematuria and the level of estimated glomerular filtration rate (eGFR) were significantly lower than those in the NTN group (all P<0.001). For the aspect of light microscope pathological manifestations, IgAN-HTN group exhibited more severe histological lesions including glomerular sclerosis, renal tubular atrophy or renal interstitial fibrosis, interstitial vascular injury than IgAN-NTN group (all P<0.05). Immunofluorescence examination results showed that the deposition ratio of C1q in IgAN-HTN group was higher than that in IgAN-NTN group (P=0.015). By employing Kaplan-Meier method, the cumulative renal survival rate in the HTN group was much lower than that in the NTN group (Log-rank test: χ2=6.456, P=0.011). For the patients in IgAN-HTN group, the cumulative renal survival rate in the dyslipidemia group was much lower than that in the ortholiposis group (Log-rank test: χ2=5.093, P=0.024). There was no significant difference in the cumulative renal survival rate between the blood pressure control group and the unqualified group (Log-rank test: χ2=1.036, P=0.309). As a result of univariate and multivariable Cox regression analysis, total cholesterol, eGFR and 24 h urinary protein were risk factors for renal progression of IgAN patients with hypertension.@*Conclusions@#The clinical manifestations and renal pathological changes in patients with IgAN-HTN are more serious than those in IgAN-NTN patients, which result in worse prognosis. IgAN-HTN patients should be paid more attention to the management of serum lipid level during treatment and follow-up.

Analysis of the clinical pathological characteristics and prognosis of primary IgA nephropathy with hypertension / 中华肾脏病杂志

Objective To investigate the clinic-pathological features and prognostic risk factors of IgA nephropathy (IgAN) with hypertension (HTN). Methods Primary IgAN patients diagnosed with biopsy from January 2016 to December 2017 were recruited. Patients were divided into IgAN with normal blood pressure (IgAN-NTN) group and IgAN with hypertension (IgAN-HTN) group based on the pressure value when performing the kidney biopsy. The clinical and pathological data were collected and compared between the two groups. Kaplan-Meier method was conducted for renal results, whereas the Cox regression model was exploited to analyze the prognostic factors in the progression of IgAN-HTN patients. Results The total number of enrolled patients was 275 cases, 170 (61.82％) of which had normal pressure and 105 individuals (38.18％) resulted in hypertension.The IgAN-HTN group in terms of male proportion, age, systolic pressure, diastolic pressure, serum urea nitrogen, serum creatinine, serum uric acid, 24 h urinary protein, triacylglycerol, complement C4 and so on were higher than those in the IgAN-NTN group (all P<0.05). The incidence of gross hematuria and the level of estimated glomerular filtration rate (eGFR) were significantly lower than those in the NTN group (all P<0.001). For the aspect of light microscope pathological manifestations, IgAN-HTN group exhibited more severe histological lesions including glomerular sclerosis, renal tubular atrophy or renal interstitial fibrosis, interstitial vascular injury than IgAN - NTN group (all P<0.05). Immunofluorescence examination results showed that the deposition ratio of C1q in IgAN-HTN group was higher than that in IgAN-NTN group (P=0.015). By employing Kaplan-Meier method, the cumulative renal survival rate in the HTN group was much lower than that in the NTN group (Log-rank test:χ2=6.456, P=0.011). For the patients in IgAN-HTN group, the cumulative renal survival rate in the dyslipidemia group was much lower than that in the ortholiposis group (Log-rank test: χ2=5.093, P=0.024). There was no significant difference in the cumulative renal survival rate between the blood pressure control group and the unqualified group (Log-rank test: χ2=1.036, P=0.309). As a result of univariate and multivariable Cox regression analysis, total cholesterol, eGFR and 24 h urinary protein were risk factors for renal progression of IgAN patients with hypertension. Conclusions The clinical manifestations and renal pathological changes in patients with IgAN-HTN are more serious than those in IgAN-NTN patients, which result in worse prognosis. IgAN-HTN patients should be paid more attention to the management of serum lipid level during treatment and follow-up.

Metabolic profiles of Cuibi-1 and Zhongyan-100 flue-cured tobacco leaves in different growing regions by gas chromatography/mass spectrometry.

The metabolic profiles of tobacco leaves of two differential Chinese cultivars from different growing regions were analysed using gas chromatography-mass spectrometry (GC-MS). The results of principal component analysis, partial least-squares discriminant analysis and hierarchical cluster analysis showed significant differences in metabolome among three groups, identified 24 differential metabolites, and analysed the metabolic pathway in which the metabolites were involved. Among them, 13 metabolites were associated with geographical regions, including seven organic and fatty acids, four carbohydrates and two secondary metabolites. Four amino acids and two monosaccharides were associated with cultivars and the remaining five metabolites were associated with both. The relationships among the differential metabolites and the distinct characteristics of environment and cultivar were further discussed. In addition, correlation analysis indicated that most of the differential carbohydrates were negatively correlated with the differential amino acids and organic acids. Taken together, this study demonstrates the metabolite differences between two cultivars in different regions, and highlights the effect of environment and cultivar on tobacco leaf metabolism.

Prevalence, risk factors, and prognosis of orthostatic hypotension in diabetic patients: A systematic review and meta-analysis.

BACKGROUND: Orthostatic hypotension (OH) is a major clinical sign of cardiovascular autonomic dysfunction in diabetic patients. Our aim was to quantitatively evaluate the prevalence and risk factors of OH in patients with diabetes mellitus (DM) and assess its prognosis. METHODS: A comprehensive search of the PubMed, Embase, China National Knowledge Infrastructure, VIP Chinese Journal, Wanfang, and SINOMED databases was conducted for related published work up to September 25, 2016, and manually searched eligible studies from the references in accordance with the inclusion criteria. RESULTS: We included 21 studies in the analysis, with a total sample size of 13,772. The pooled prevalence of OH in DM was 24% (95% confidence interval [CI]: 19-28%). Potential risk factors, that is, glycosylated hemoglobin A (HbA1c) (odds ratio [OR], 1.13, 95% CI, 1.07-1.20), hypertension (OR, 1.02, 95% CI, 1.01-1.02), and diabetic nephropathy (OR, 2.37, 95% CI, 1.76-3.19), were significantly associated with OH in DM. In addition, the prognosis of OH in DM was associated with higher risk of total mortality and cardiovascular events. CONCLUSION: The pooled prevalence of OH in DM appears high. HbA1c, hypertension, and diabetic nephropathy are risk factors for OH in DM. OH indicates poor prognosis in diabetic patients. Attention should be focused on diabetic patients with the stated risk factors to prevent OH.

Interleukin-17 augments tumor necrosis factor α-mediated increase of hypoxia-inducible factor-1α and inhibits vasodilator-stimulated phosphoprotein expression to reduce the adhesion of breast cancer cells.

Interleukin-17 (IL-17) and tumor necrosis factor (TNF)-α are able to cooperatively alter the expression levels of a number of genes. In the present study, the mRNA expression levels of hypoxia-inducible factor (HIF)-1α were analyzed in MDA-MB-231 breast cancer cells following treatment with IL-17, TNF-α or the combination of IL-17 and TNF-α. The protein expression levels of HIF-1α and vasodilator-stimulated phosphoprotein (VASP) were evaluated using western blot analysis. The adhesive ability of the cells was determined using an MTT assay following treatment with HIF-1α-small interfering RNA and short hairpin RNA-VASP that were used to suppress the expression levels of HIF-1α and VASP protein, respectively. These results demonstrated that IL-17 augmented TNF-α-induced gene expression of HIF-1α. The combination of IL-17 and TNF-α promoted an increase in HIF-1α expression and a decrease in VASP expression and a reduction in the adhesive ability of cells. These results demonstrated that IL-17 effectively enhanced the TNF-α-induced increase in HIF-1α and inhibited VASP expression, thus reducing the adhesion of MDA-MB-231 cells.

Artesunate supresses NF-κB and MCP-1 expressions in high glucose-induced rat mesangial cell proliferation model / 天津医药

Objective To investigate the effects of artesunate (Art) on cell proliferation, apoptosis, nuclear factor (NF)-κB and monocyte chemotactic protein 1 (MCP-1) expressions induced by high glucose in rat renal mesangial cells (HBZY-1), and the mechanism thereof. Methods HBZY-1 cells were cultured and divided into normal glucose group (5.6 mmol/L), high glucose group (25 mmol/L) and high glucose with different concentrations of Art (10 mg/L, 20 mg/L, 30 mg/L) groups. MTT assay was used to detect the cell proliferation after 48 h. The apoptotic rate was evaluated by flow cytometry with Annexin V-FITC/PI double stains. The protein levels of NF-κB and MCP-1 in the cell culture supernatant were determined using ELISA. Results High glucose induced apoptosis and proliferation in HBZY-1 cells, and the expressions of NF-κB and MCP-1 in the supernatant were also increased (P<0.05). After treatment with Art, the proliferation was obviously abolished, and the apoptosis was increased, and the expressions of NF-κB and MCP-1 in the supernatant were decreased in HBZY-1 cells. The effects of Art showed a dose-dependent manner (P<0.05). Conclusion Artesunate treatment can reverse the effect of high glucose in HBZY-1 cells in a dose-dependent manner, which may provide a new therapeutic strategy for diabetic nephropathy.