The role of microbial metabolites in diabetic kidney disease.

Background: Growing evidence suggests a complex bidirectional interaction between gut microbes, gut-derived microbial metabolites, and diabetic kidney disease (DKD), known as the "gut-kidney axis" theory. The present study aimed to characterize the role of microbial metabolites in DKD. Methods: Six-week-old db/db and littermate db/m mice were raised to 20 weeks old. The serum, urine, feces, liver, perinephric fat, and kidney were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based metabolomic analyses. Results: The db/db mice showed obvious pathological changes and worse renal functions than db/m mice. Indoleacetaldehyde (IAld) and 5-hydroxy-l-tryptophan (5-HTP) in kidney samples, and serotonin (5-HT) in fecal samples were increased in the db/db group. Phosphatidylcholine (PC), phosphatidate (PA), and 1-acylglycerophosphocholine (lysoPC) were decreased in liver and serum samples of the db/db group, while PC and lysoPC were decreased in kidney and perinephric fat samples. Suggested metabolomic homeostasis was disrupted in DKD mice, especially glycerophospholipid and tryptophan metabolism, which are closely related to the gut microbiome. Conclusions: Our findings reveal the perturbation of gut microbial metabolism in db/db mice with DKD, which may be useful for building a bridge between the gut microbiota and the progression of DKD and provide a theoretical basis for the intestinal treatment of DKD.

[Regularities of acupoint compatibility and application characteristics of methods of needling and moxibustion in the treatment of ankle sprain based on complex network analysis].

OBJECTIVE: To analyze the compatibility regularities of acupoints and the application characteristics of needling-moxibustionmethods in the treatment of ankle sprain by using complex network technology, so as to provide the basis and treatment ideas. METHODS: The clinical research articles on acupuncture treatment of ankle joint sprain published from November 2011 to November 2021 were retrieved from databases of CNKI, Wanfang Data knowledge service platform, VIP information Chinese journal service platform and PubMed by using key words of "acupuncture""moxibustion" "acupuncture and moxibustion" "ankle injury" "ankle sprain" "injured ankle" and "syndesmotic injuries". After screening these articles according to our inclusion and exclusion criteria, a database of acupuncture treatment of ankle sprain was established. Then, analysis on the occurrence frequency of acupoints and their related meridians, and methods of needling manipulation, and the association rule analysis (quantitative analysis) about the closeness between acupoints, and the degree of support and confidence coefficient were conducted for acquiring the acupoint combinations with higher correlation in the compatibility using Apriori algorithm after modeling (with IBM SPSS Modeler18.0 software). Gephi 0.9.2 software was used to make complex network analysis, for which "k-core hierarchical analysis" and "community analysis" were used as the methods to analyze the network structure of acupoints, and the confidence value was used as the index to measure the importance of acupoints. RESULTS: A total of 201 articles meeting the criteria were collected, including 196 articles in Chinese and 5 in English. A total of 236 acupuncture prescriptions were extracted, involving 61 acupoints, with a total frequency of occurrence being 846. The top 10 acupoints were Ashi point, Kunlun (BL60), Jiexi (ST41), Qiuxu (GB40), Shenmai (BL62), Yanglingquan (GB34), Taixi (KI3), Zhaohai (KI6), Xuanzhong (GB39) and Shangqiu (SP5), with the occurrence frequency being 109, 79, 70, 68, 63, 59, 53, 52, 37 and 34, respectively. The results of descriptive analysis showed that the top 5 meridians were Gallbladder Meridian of Foot-shaoyang, Bladder Meridian of Foot-taiyang, Kidney Meridian of Foot-shaoyin, Stomach Meridian of Foot-yangming and Spleen Meridian of Foot-taiyin, with the frequency being 181, 153, 116, 105 and 53, respectively. Complex network analysis displayed that after "k-core hierarchical analysis" and "Community division", two communities were reserved, mainly involving 15 core acupoints such as Ahshi point, GB40, ST14, BL62, GB34, KI6, BL60, KI3, GB39, Zusanli (ST36), SP5; Taichong (LR3), Zulinqi (GB41), Sanyinjiao (SP6) and Rangu (KI2). The results of association rule analysis showed that the most relevant acupoint combination is "BL60-ST41" (support degree 34.83％), followed by "BL60-KI3" (support degree 26.37%), reflecting the principle of selection of local acupoint for ankle sprain. The therapeutic methods are filiform needle acupuncture, and the reducing technique and uniform reinforcing and reducing manipulation are the most commonly used approaches, but the reinforcing method is rarely used. CONCLUSION: In the treatment of ankle sprain, local acupoints and Ashi points are mainly used, in combination with reducing or uniform reinforcing and reducing manipulations, as well as the method of needling and moxibustion, which provides a good reference for clinical practice.

Anthocyanin improves kidney function in diabetic kidney disease by regulating amino acid metabolism.

BACKGROUND: Diabetic kidney disease (DKD) is among the most important causes for chronic kidney disease. Anthocyanins (ANT) are polyphenolic compounds present in various food and play an important role in ameliorating hyperglycemia and insulin sensitivity. However, the effects of ANT in DKD are still poorly understood. This study aimed to investigate the effect of ANT (cyanidin-3-O-glucoside [C3G]) on the renal function of DKD, and whether the anti-DKD effect of ANT is related to metabolic pathways. METHODS: To explore the role of ANT in DKD, we performed the examination of blood glucose, renal function, and histopathology. As for the mechanism, we designed the label-free quantification proteomics and nontargeted metabolomics analysis for kidney and serum. Subsequently, we revealed the anti-DKD effect of ANT through the bioinformatic analysis. RESULTS: We showed that the fasting blood glucose level (- 6.1 mmol/L, P = 0.037), perimeter of glomerular lesions (- 24.1 µm, P = 0.030), fibrosis score of glomerular (- 8.8%, P = 0.002), and kidney function (Cystatin C: - 701.4 pg/mL, P = 0.043; urine creatinine: - 701.4 mmol/L, P = 0.032) were significantly alleviated in DKD mice after ANT treatment compared to untreated in the 20th week. Further, proteins and metabolites in the kidneys of DKD mice were observed to be dramatically altered due to changes in amino acid metabolism with ANT treatment; mainly, taurine and hypotaurine metabolism pathway was upregulated (P = 0.0001, t value = 5.97). Furthermore, upregulated tryptophan metabolism (P < 0.0001, t value = 5.94) and tyrosine metabolism (P = 0.0037, t value = 2.91) pathways had effects on serum of DKD mice as responsed ANT regulating. CONCLUSIONS: Our results suggested that prevention of the progression of DKD by ANT could be related to the regulation of amino acid metabolism. The use of dietary ANT may be one of the dietary strategies to prevent and treat DKD.

[Visual analysis of the acupoint prescription characteristics of acupuncture and moxibustion in treatment of rheumatoid arthritis].

Using the complex network technology, the characteristics of the core acupoint prescriptions and the application of acupuncture-moxibustion techniques were analyzed in treatment of rheumatoid arthritis (RA) so as to provide the evidences for acupoint selection and therapeutic methods for RA treated with acupuncture and moxibustion. The articles of acupuncture and moxibustion for treatment of RA in recent 20 years were collated and imported, and the database of the acupoint prescriptions was developed. Using Cytoscape 3.9.2 software, the acupoints in the prescriptions were visualized for the common occurrence network analysis. The association rule analysis was performed with IBM SPSS Modeler 18.0 software and the complex network analysis was by Gephi 0.9.2 software. A total of 798 articles were screened, in which, 3 258 prescriptions were extracted with 253 acupoints involved. The analysis of acupoint selection was conducted in terms of syndrome/pattern differentiation, acupoint locations and main acupoints, and therapeutic methods. The results showed that the most common TCM syndromes of RA included painful bi syndrome, wandering bi syndrome, fixed bi syndrome and bi syndrome due to wind, damp and heat. Regarding the core combination of acupoints, painful bi syndrome: Guanyuan (CV 4) and Shenshu (BL 23); fixed bi syndrome: Yinlingquan (SP 9), Sanyinjiao (SP 6), Zusanli (ST 36), Pishu (BL 20) and Fenglong (ST 40); wandering bi syndrome: Fengchi (GB 20), Geshu (BL 17), Fengmen (BL 12), Xuehai (SP 10) and Waiguan (TE 5); bi syndrome due to wind, damp and heat: Dazhui (GV 14), Quchi (LI 11) and Hegu (LI 4). Regarding the acupoint locations, the acupoints located in the upper limbs, lower limbs and spinal region were generally selected. Quchi (LI 11) was one of the main acupoints in prescriptions with the highest use frequency. Zusanli (ST 36) and Shenshu (BL 23) presented the highest co-occurrence intensity, while Zusanli (ST 36) and Quchi (LI 11) indicated the highest correlation. The treatment of acupuncture-moxibustion for RA is generally complied with the principle as "the synthesis of main acupoints, supplementary acupoints in local affected area and those based on syndrome differentiation". Warm needling and the combination of acupuncture and herbal medication are the most common therapeutic methods for RA.

SGLT2 inhibitors improve kidney function and morphology by regulating renal metabolic reprogramming in mice with diabetic kidney disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. SGLT2 inhibitors are clinically effective in halting DKD progression. However, the underlying mechanisms remain unclear. The serum and kidneys of mice with DKD were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based metabolomic and proteomic analyses. Three groups were established: placebo-treated littermate db/m mice, placebo-treated db/db mice and EMPA-treated db/db mice. Empagliflozin (EMPA) and placebo (10 mg/kg/d) were administered for 12 weeks. EMPA treatment decreased Cys-C and urinary albumin excretion compared with placebo by 78.60% and 57.12%, respectively (p < 0.001 in all cases). Renal glomerular area, interstitial fibrosis and glomerulosclerosis were decreased by 16.47%, 68.50% and 62.82%, respectively (p < 0.05 in all cases). Multi-omic analysis revealed that EMPA treatment altered the protein and metabolic profiles in the db/db group, including 32 renal proteins, 51 serum proteins, 94 renal metabolites and 37 serum metabolites. Five EMPA-related metabolic pathways were identified by integrating proteomic and metabolomic analyses, which are involved in renal purine metabolism; pyrimidine metabolism; tryptophan metabolism; nicotinate and nicotinamide metabolism, and glycine, serine and threonine metabolism in serum. In conclusion, this study demonstrated metabolic reprogramming in mice with DKD. EMPA treatment improved kidney function and morphology by regulating metabolic reprogramming, including regulation of renal reductive stress, alleviation of mitochondrial dysfunction and reduction in renal oxidative stress reaction.

Effects of laminarin zwitterionic carboxylate and sulfonate on the intestinal barrier function and gut microbiota.

Ulcerative colitis (UC) has become a global chronic disease that keeps increasing. This study was to explore the treatment effectiveness of two functional zwitterionic laminarins, zwitterionic sulfonate (LZS) and zwitterionic carboxylate (LZC), in dextran sulfate sodium (DSS) induced mouse model. FT-IR and NMR techniques were used to characterize the aforementioned functional zwitterion. Compared to UC mice, the composition and diversity of gut microbiota were significantly increased in the treated mice. Specifically, the composition of Bacteroidetes increased and the level of Firmicutes decreased. Moreover, we demonstrated the alleviation of colitis by LZS and LZC reflected by the improved integrity of intestinal mucosa, which includes increased number of goblet cells, mucin protein production, maintenance of collagens, as well as the lower extent of intestinal fibrosis. These findings indicated the potentials of LZC and LZS as promising agents to prevent colitis via adjusting gut microbiota and maintaining intestinal barrier integrity.

Day-by-day blood pressure variability in hospitalized patients with COVID-19.

In a retrospective analysis, the authors investigated day-by-day blood pressure variability (BPV) and its association with clinical outcomes (critical vs. severe and discharged) in hospitalized patients with COVID-19. The study participants were hospitalized in Tongji Hospital, Guanggu Branch, Wuhan, China, between February 1 and April 1, 2020. BPV was assessed as standard derivation (SD), coefficient of variation (CV), and variability independent of mean (VIM). The 79 participants included 60 (75.9%) severe patients discharged from the hospital after up to 47 days of hospitalization, and 19 (24.1%) critically ill patients transferred to other hospitals for further treatment (n = 13), admitted to ICU (n = 3) or died (n=3). Despite similar use of antihypertensive medication (47.4% vs. 41.7%) and mean levels of systolic/diastolic blood pressure (131.3/75.2 vs. 125.4/77.3 mmHg), critically ill patients, compared with severe and discharged patients, had a significantly (p ≤ .04) greater variability of systolic (SD 14.92 vs. 10.84 mmHg, CV 11.39% vs. 8.56%, and VIM 15.15 vs. 10.75 units) and diastolic blood pressure (SD 9.38 vs. 7.50 mmHg, CV 12.66% vs. 9.80%, and VIM 9.33 vs. 7.50 units). After adjustment for confounding factors, the odds ratios for critical versus severe and discharged patients for systolic BPV were 3.41 (95% confidence interval [CI] 1.20-9.66, p = .02), 4.09 (95% CI 1.14-14.67, p = .03), and 2.81 (95% CI 1.12-7.05, p = .03) for each 5-mmHg increment in SD, 5% increment in CV, and 5-unit increment in VIM, respectively. Similar trends were observed for diastolic BPV indices (p ≤ .08). In conclusion, in patients with COVID-19, BPV was greater and associated with worse clinical outcomes.

hAECs and their exosomes improve cardiac function after acute myocardial infarction in rats.

BACKGROUND: Human amniotic epithelial cells (hAECs) are seed cells used to treat acute myocardial infarction (AMI), but their mechanism remains unclear. METHODS: We cultured hAECs and extracted exosomes from culture supernatants. Next, we established a stable AMI model in rats and treated them with hAECs, exosomes, or PBS. We assess cardiac function after treatment by echocardiography. Additionally, heart tissues were collected and analyzed by Masson's trichrome staining. We conducted the tube formation and apoptosis assays to explore the potential mechanisms. RESULTS: Cardiac function was improved, and tissue fibrosis was decreased following implantation of hAECs and their exosomes. Echocardiography showed that the EF and FS were lower in the control group than in the hAEC and exosome groups, and that the LVEDD and LVESD were higher in the control group (P<0.05). Masson's trichrome staining showed that the fibrotic area was larger in the control group. Tube formation was more efficient in the hAEC and exosome groups (P<0.0001). Additionally, the apoptosis rates of myocardial cells in the hAEC and exosome groups were significantly decreased (P<0.0001). CONCLUSIONS: hAECs and their exosomes improved the cardiac function of rats after AMI by promoting angiogenesis and reducing the apoptosis of cardiac myocytes.

Flotation dynamics of metal and non-metal components in waste printed circuit boards.

Flotation is an effective and clean separation technology to realize the recovery of metal in waste printed circuit boards (WPCBs). The flotation kinetic of metal and non-metal components was concerned in this study. In addition, the loading of bubbles, the collision and shedding of particles and bubbles were used to assist in proving the particle dynamics results. By analyzing the force on the particles, the load of bubbles on particles was analyzed, and the appropriate volume ratio of bubbles to particles was 1.5-8.0, depending on the particle density. Moreover, Clift model and Schiller-Naumann model has high fitting accuracy for the final bubble velocity. In addition, metal particles have greater settling velocity, which results in shorter collision time with bubbles. In the process of bubble-particle rising, the shedding probability gradually decreases, and the shedding probability of metal particles is much higher than that of non-metal particles. The results of flotation kinetics show that the removal of impurity particles represented by silicon mainly occurs in the initial stage of flotation process. The loss of copper increases with flotation time and collector dosage. This study reveals the flotation kinetics of particles from the perspectives of bubble loading, bubble-particle collision and shedding.

Rs10757274 gene polymorphisms in coronary artery disease: A systematic review and a meta-analysis.

BACKGROUND: It has been reported the rs10757274 SNP (present on locus 9p21 in the gene for CDKN2BAS1) might be associated with susceptibility to coronary artery disease (CAD). Owing to mixed and inconclusive results, we conducted a meta-analysis to investigate the association between rs10757274 polymorphism and the risk of CAD. OBJECTIVES: The present study aimed to investigate the relationship between rs10757274 polymorphism and the risk of CAD. METHODS: All studies of the rs10757274 SNP with CAD that were published between 2007 and 2018 were retrieved from the PubMed database. Meta-analysis was performed with Stata 14.0 software. The effect size of the rs10757274 SNP with CAD risk was assessed based on the odds ratios (ORs) with calculation of 95% confidence interval (CI). RESULTS: Eleven studies including 52,209 subjects (cases: 7990, controls: 44,219) were included in the final data combination. Pooled overall analyses showed that rs10757274 (allele model: P < .001; dominant model: P < .001; recessive model: P < .001; Heterozygote codominant: P = .002; Homozygote codominant: P < .001) polymorphisms were significantly associated with the likelihood of CAD. Significant heterogeneity between individual studies appears in all 5 models. Further subgroup analyses revealed that rs10757274 polymorphisms were all significantly correlated with the likelihood of CAD and no heterogeneity were observed in West Asians. CONCLUSIONS: Our findings indicated that rs10757274 polymorphisms may serve as genetic biomarkers of CAD, especially in West Asians.

Spectral Analysis of Epidemic Thresholds of Temporal Networks.

Many complex systems can be modeled as temporal networks with time-evolving connections. The influence of their characteristics on epidemic spreading is analyzed in a susceptible-infected-susceptible epidemic model illustrated by the discrete-time Markov chain approach. We develop the analytical epidemic thresholds in terms of the spectral radius of weighted adjacency matrix by averaging temporal networks, e.g., periodic, nonperiodic Markovian networks, and a special nonperiodic non-Markovian network (the link activation network) in time. We discuss the impacts of statistical characteristics, e.g., bursts and duration heterogeneity, as well as time-reversed characteristic on epidemic thresholds. We confirm the tightness of the proposed epidemic thresholds with numerical simulations on seven artificial and empirical temporal networks and show that the epidemic threshold of our theory is more precise than those of previous studies.

Role of Endothelial Nitric Oxide Synthase Polymorphisms in Atrial Fibrillation: A PRISMA-Compliant Meta-Analysis.

BACKGROUND Research interest in endothelial nitric oxide synthase(eNOS) polymorphisms and atrial fibrillation (AF) has grown in last recent years, but the results of individual studies are inconsistent due to their small sample sizes. MATERIAL AND METHODS We searched databases for eligible studies on eNOS and AF, extracted the relevant data, and rigorously screened them according to inclusion and exclusion criteria. Then, we evaluated the study quality according to the Newcastle-Ottawa scale score, and we pooled the odds ratios (ORs) and 95% confidence intervals (CIs) by using a random-effects model or fixed-effects model based on inter-study heterogeneity. In addition, we performed subgroup analysis and sensitivity analysis and assessed publication bias. RESULTS According to the inclusion and exclusion criteria, we finally found 8 studies in this search. The recessive (OR=0.81; 95% CI=0.67 to 0.97; p=0.988; I²=0.0%) model showed that the eNOS 786T/C polymorphism was relevant to AF. We also found that the eNOS 786T/C polymorphism decreases the risk of AF, especially in white people (OR=0.81; 95% CI=0.67 to 0.97; P=0.023 for recessive model) and in the control population (OR=0.79; 95% CI=0.65 to 0.97; P=0.022 for recessive model). We found no obvious publication bias. CONCLUSIONS The eNOS gene loci 786T/C polymorphism is relevant to the risk of AF. Our results suggest that the 786T/C polymorphism significantly decreases AF risks in white people and control populations. Larger studies are required for further evaluation.

Diagnostic value of cadmium-zinc-telluride myocardial perfusion imaging versus coronary angiography in coronary artery disease: A PRISMA-compliant meta-analysis.

BACKGROUND: Rapid progress has been made in research of cadmium-zinc-telluride (CZT) technology in the last few years, which might serve as a new method to diagnose coronary artery disease. However, compared with coronary angiography, the diagnostic value of CZT is still controversial. We aimed to evaluate diagnosis value of coronary angiography versus CZT in coronary artery disease. METHODS: We searched the database for eligible researches associated with CZT- myocardial perfusion imaging (MPI) and invasive coronary angiography, extracted the relevant data, and rigorously screened it according to the inclusion and exclusion criteria. The accuracy indicators included sensitivity, specificity, accuracy, positive and negative likelihood ratios. RESULTS: According to the inclusion and exclusion criteria, we finally found 20 studies containing 2350 patients in this search. Pooled results showed that sensitivity of CZT-MPI was 0.84% and 95% confidence interval (95% CI): 0.78 to 0.89, specificity was 0.72, 95% CI (0.62-0.76), the specificity was lower apparently. The positive likelihood ratio was 3.0, 95% CI (2.4-3.8), the negative likelihood ratio was 0.22, 95% CI (0.16-0.31), diagnostic odds ratio was 14, 95% CI (7.84-17.42). CONCLUSION: This meta-analysis showed that CZT-MPI had satisfactory sensitivity and specificity for diagnosing coronary artery disease. Larger studies are required for further evaluation.

Astragaloside IV alleviates heart failure by promoting angiogenesis through the JAK-STAT3 pathway.

CONTEXT: Heart failure (HF) is one of the most serious diseases worldwide. Astragaloside IV (ASI) is widely used for the treatment of cardiovascular disease in China. OBJECTIVE: To evaluate the protective effect of ASI on the HF in a Sprague-Dawley rat model of left coronary artery ligation, and investigate the angiogenesis-related mechanisms. MATERIALS AND METHODS: Left coronary artery was ligated to induce a rat model of HF, and the rats were treated with vehicle (saline) or different doses of ASI (0.1, 0.3 and 1 mg/kg/day) by oral gavage for 6 weeks. Cardiac function was evaluated by echocardiography. Infarct size was determined by triphenyltetrazolium chloride staining. Cardiac vascular density was analyzed by microangiography. Real-time PCR, Western blot and chromatin immunoprecipitation were performed to investigate the mechanisms. RESULTS: ASI treatment improved the body weight and survival rate of HF rats, as well as the cardiac function of HF rats, with significantly improved ejection fraction (75.27 ± 5.75% vs. 36.26 ± 4.14%) and fractional shortening (45.39 ± 3.66% vs. 17.88 ± 1.32%). ASI reduced the infarct size of the HF rats by 47%. ASI promoted angiogenesis, with increased vascular density (2.08-fold) and induced mRNA expression of CD31 (1.81-fold) and VEGF (2.70-fold) in the ischemic heart. Furthermore, ASI induced the phosphorylation of JAK (1.89-fold) and STAT3 (2.95-fold), as well as the activity of VEGF promoter which was regulated by STAT3. DISCUSSION AND CONCLUSIONS: ASI alleviated HF by promoting angiogenesis through JAK-STAT3 pathway, providing novel alternative strategies to prevent HF in the future.

A retrospective study of traditional Chinese medicine as an adjunctive therapy for patients with chronic heart failure.

This study retrospectively evaluated the effectiveness and safety of traditional Chinese medicine Shenqilixin Formula (SQLXF) as an adjunctive intervention for treating patients with chronic heart failure (CHF).This retrospective study included 135 patients with CHF. They were allocated to a treatment group or a control group according to the different treatments they received. Seventy five patients in the treatment group underwent SQLXF plus routine treatment, while 60 subjects in the control group received routine treatment only. The primary outcome was cardiac function. It was measured by the left ventricular end diastolic diameter (LVDD), left ventricular ejection fraction (LVEF), cardiac output (CO), every cardiac output (ECO), and cardiac index (CI). The secondary outcome included motor function. It was measured by the standard 6-MinuteWalk Test (6MWT). In addition, adverse events (AEs) were also recorded.Compared to subjects in the control group, patients in the treatment group revealed greater effectiveness in cardiac function, measured by LVEF (P < .05), CO (P < .05), and ECO (P < .05), and motor function, measured by the 6MWT scale (P < .05). Moreover, no significant differences of AEs were found between the 2 groups.SQLXF as an adjunctive therapy to routine treatment may help to improve both cardiac and motor function in patients with CHF.

Targeting the RhoA-ROCK pathway to regulate T-cell homeostasis in hypoxia-induced pulmonary arterial hypertension.

BACKGROUND: Hypoxic pulmonary arterial hypertension (PAH) is a crippling disease with limited therapeutic methods. The imbalance of T helper 17 cell (Th17)/regulatory T cell (Treg) plays an important role in the development of Hypoxic PAH. However, whether targeting the ras homolog family member A-Rho kinase (RhoA-ROCK) pathway (activation and inhibition) by lysophosphatidic acid (LPA) and fasudil (FSD) regulate T-cell homeostasis in Hypoxic PAH remain unknown. OBJECTIVE: To examine the effects of LPA and FSD on hypoxic pulmonary vascular remodeling and homeostasis of Th17/Treg cells in Hypoxic PAH. METHODS: Rats were exposed to hypoxia (10 ±â€¯0.5% O2) to induce Hypoxic PAH. The experiments consists of two parts. Forty rats were randomly divided into four groups (n = 10): normoxia group, normoxia + LPA group, hypoxia group and hypoxia + LPA group. Thirty rats were randomly divided into another three groups (n = 10): normoxia group, hypoxia group, and hypoxia + FSD group. Rats in normoxia + LPA group and hypoxia + LPA group were intraperitoneally injected 40 µg/kg LPA daily. Rats in hypoxia + FSD group were intraperitoneally injected 30 mg/kg fasudil daily. The effects of LPA and FSD on the development of hypoxic PAH and right ventricle (RV) hypertrophy, on pulmonary vascular remodeling, and on changes of Th17/Treg cells and levels of interleukin-17 (IL-17) and IL-10 were examined. RESULTS: PAH and RV hypertrophy occurred in rats exposed to hypoxia. LPA exacerbated hypoxic pulmonary vascular remodeling and FSD inhibited it. LPA increased Th17/Treg imbalance in peripheral blood and spleen. However, after treatment with FSD, hypoxic PAH rats showed an obvious reduction of Th17 cells as well as an increase of Treg cells. LPA increased the expression of phosphorylated-signal transducer and activator of transcription 3 (p-STAT3) and reduced the p-STAT5 in peripheral blood and spleen in hypoxic PAH rats. The expression of p-STAT3 and p-STAT5 in hypoxic PAH rats treated with FSD showed opposite changes. LPA increased the expression of IL-17 and reduced the IL-10 in small intrapulmonary arteries and serum in hypoxic PAH. However, the expression of IL-17 and IL-10 in hypoxic PAH rats treated with FSD showed opposite changes. CONCLUSIONS: Activation and inhibition of RhoA-ROCK pathway by LPA and FSD modulated the homeostasis of Th17/Treg cells via regulating STAT3/STAT5 phosphorylation in hypoxic PAH. Thus, Apart from influence of pulmonary vascular remodeling, regulation of Th17/Treg homeostasis by RhoA-ROCK pathway play a key role in hypoxic PAH.

[Study on UV and H2O2 combined inactivation of E. coli in drinking water].

The inactivation effect of E. coli with both UV irradiation and hydrogen peroxide disinfection individually and in different combination modes was investigated. The results showed that hydrogen peroxide alone caused hardly any inactivation of E. coli. Only 0.02 lg inactivation was achieved by hydrogen peroxide with concentration of 20 mg x L(-1) and contact time of 30 min. UV irradiation was able to inactivate E. coli to a certain extent. The inactivation reached 4.51 lg at a UV dose of 10 mJ x cm(-2). The combination of UV and H2O2 could significantly improve the inactivation effect and the different combination modes affected the inactivation effect. The inactivation effect of UV-H2O2 was better than that of H2O2 -UV. The inactivation was increased by 0.09, 0.35, 0.38, 0.68 lg and 0.01, 0.07, 0.14, 0.53 lg when compared to the treatment with solely UV irradiation, respectively, at UV dose of 5 mJ x cm(-2) with hydrogen peroxide at contact time of 2.5, 5, 10, 20 minutes. UV/H2O2 achieved better results than sequential disinfection. The inactivation was enhanced by 0.43 lg and 0.58 lg when compared to UV-H2O2 and H2O2-UV, respectively, at UV dose of 5 mJ x cm(-2) with hydrogen peroxide at contact time of 20 minutes. The inactivation of E. coli increased with the enhancement of UV radiation intensity.