Unveiling the interplay between mutational signatures and tumor microenvironment: a pan-cancer analysis.

Background: While recent studies have separately explored mutational signatures and the tumor microenvironment (TME), there is limited research on the associations of both factors in a pan-cancer context. Materials and methods: We performed a pan-cancer analysis of over 8,000 tumor samples from The Cancer Genome Atlas (TCGA) project. Machine learning methods were employed to systematically explore the relationship between mutational signatures and TME and develop a risk score based on TME-associated mutational signatures to predict patient survival outcomes. We also constructed an interaction model to explore how mutational signatures and TME interact and influence cancer prognosis. Results: Our analysis revealed a varied association between mutational signatures and TME, with the Clock-like signature showing the most widespread influence. Risk scores based on mutational signatures mainly induced by Clock-like and AID/APOBEC activity exhibited strong pan-cancer survival stratification ability. We also propose a novel approach to predict transcriptome decomposed infiltration levels using genome-derived mutational signatures as an alternative approach for exploring TME cell types when transcriptome data are unavailable. Our comprehensive analysis revealed that certain mutational signatures and their interaction with immune cells significantly impact clinical outcomes in particular cancer types. For instance, T cell infiltration levels only served as a prognostic biomarker in melanoma patients with high ultraviolet radiation exposure, breast cancer patients with high homologous recombination deficiency signature, and lung adenocarcinoma patients with high tobacco-associated mutational signature. Conclusion: Our study comprehensively explains the complex interplay between mutational signatures and immune infiltration in cancer. The results highlight the importance of considering both mutational signatures and immune phenotypes in cancer research and their significant implications for developing personalized cancer treatments and more effective immunotherapy.

Advancements in MAFLD Modeling with Human Cell and Organoid Models.

Metabolic (dysfunction) associated fatty liver disease (MAFLD) is one of the most prevalent liver diseases and has no approved therapeutics. The high failure rates witnessed in late-phase MAFLD drug trials reflect the complexity of the disease, and how the disease develops and progresses remains to be fully understood. In vitro, human disease models play a pivotal role in mechanistic studies to unravel novel disease drivers and in drug testing studies to evaluate human-specific responses. This review focuses on MAFLD disease modeling using human cell and organoid models. The spectrum of patient-derived primary cells and immortalized cell lines employed to model various liver parenchymal and non-parenchymal cell types essential for MAFLD development and progression is discussed. Diverse forms of cell culture platforms utilized to recapitulate tissue-level pathophysiology in different stages of the disease are also reviewed.

Urinary metabolomics analysis to reveal metabolic mechanism of guanxinning injection on heart failure with renal dysfunction.

Consistently, the multiple heart-kidney interactions make pharmaceutical research for cardiorenal syndrome difficult and complex. Guanxinning Injection (GXN) has been reported to provide unique advantage for treating cardiac and renal diseases compared to typical monotherapies. However, the protection mechanism of GXN is largely unknown. This study explored the acting mechanism of GXN on heart failure with renal dysfunction from a metabolic perspective. Transverse aortic constriction (TAC) surgery was performed on C57/BL/6 mice to induce heart failure with renal dysfunction. Using telmisartan as a positive control, GXN treatment was applied during the 12th to 16th week after TAC. Cardiac function and structure were examined using M-mode echocardiography, and renal function was evaluated via representative biochemical parameters and hematoxylin-eosin staining. Moreover, untargeted metabolomic analyses of urine were conducted to screen for differential substances associated with the cardiorenal protection effect of GXN. As a result, GXN provided good cardioprotective effects on left ventricular ejection fraction elevation, fractional shortening, internal diastolic, and mass maintenance. GXN also reduced TAC-induced elevation of blood urea nitrogen, and serum Cystatin C and relieved kidney pathological damage. Metabolomic analyses identified 21 differential metabolites in the TAC model group. Ten metabolites involving the metabolic pathways of carnitine synthesis, valine, leucine and isoleucine degradation, and glutamate metabolism, taurine and hypotaurine metabolism, tryptophan metabolism, arginine and proline metabolism, and purine metabolism were restored by GXN. The main cardiorenal protection mechanism of GXN was found to be related to energy metabolism and oxidative stress. Taken together, this study provides the first evidence of the metabolic protection mechanism of GXN on heart failure with renal dysfunction for the first time and provides a research basis for the application of GXN in CRS-2 pharmaceuticals.

Prevalence and Risk Factors of Restless Legs Syndrome in Hemodialysis Patients.

OBJECTIVE: The current study aimed to investigate the prevalence and risk factors of restless legs syndrome (RLS) in patients undergoing hemodialysis, as well as the mortality and risks of cardiovascular and cerebrovascular events. METHODS: A total of 354 hemodialysis patients from four hospitals were enrolled. RLS was diagnosed using the International RLS Study Group (IRLSSG) criteria. The patients were evaluated face-to-face using the IRLSSG rating scale, Epworth Sleepiness Scale (ESS), Hamilton Anxiety Scale, Hamilton Depression Scale, and Pittsburgh Sleep Quality Index (PSQI). The patients were followed up for 9 months. Death was considered an endpoint event. The cardiovascular and cerebrovascular events were investigated. RESULTS: The prevalence of RLS in hemodialysis patients was 40.7% and was associated with factors such as duration of hemodialysis, hypersensitive C-reactive protein, hyperparathyroidism, glycosylated serum protein, and erythropoietin treatment. The scores of the PSQI, ESS, and Hamilton Depression Scale in the RLS group were significantly higher than those in the non-RLS group (p < 0.05). During follow-ups, the incidence rate of cardiovascular diseases was 18.8% in the RLS group and 8.6% in the non-RLS group (p < 0.005). The IRLSSG rating scores were significantly higher in RLS patients with kidney transplantation failure compared with those without transplantation (p < 0.05). CONCLUSION: The prevalence of RLS was high in hemodialysis patients. The risk factors of RLS included duration of hemodialysis, hypersensitive C-reactive protein, hyperparathyroidism, glycosylated serum protein, and erythropoietin treatment. RLS affected sleep quality and emotion and increased the risk of cardiovascular diseases in hemodialysis patients. RLS was more severe in patients with kidney transplantation failure compared with those without transplantation.

Serum Magnesium and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND AND AIM: The study aimed to investigate the potential contributing effect of serum magnesium on mortality in maintenance hemodialysis (MHD) patients. METHODS: The patients receiving regular MHD in March 2013 were involved. Baseline data including clinical data, anthropometrics and biochemical measurement were collected. After being followed for 36 months, the time of death and reason were recorded. RESULTS: One hundred and thirty-five MHD patients were enrolled in the study and analyzed, with mean serum magnesium of 1.11 ± 0.15 mmol/l. The level of serum magnesium in 64 patients was normal (47.4%), and it was elevated in 71 of the 135 patients (52.6%). And none of MHD patients had hypomagnesemia. The levels of serum albumin (Alb), urea nitrogen, creatinine (Cr), uric acid and phosphorus were significantly higher, but high-sensitivity C-reactive protein (Hs-CRP) and lipoprotein A were significantly lower in hypermagnesemia group compared to the normal serum magnesium group (p < 0.05). Serum Alb, serum Cr, serum phosphorus and Hs-CRP were related factors of hypermagnesemia by multivariate logistic regression analysis (p < 0.05). During the 36 months of follow-up, 27 patients died (20.0%), of whom 55.6% died of cardiovascular (CV) events. Kaplan-Meier curves showed that cumulative incidence of CV mortality were significantly higher in the normal serum magnesium group than in the hypermagnesemia group (p = 0.027); however, there was no significant difference in all-cause mortality (p > 0.05). CONCLUSIONS: Serum magnesium was elevated, which was related with nutrition and inflammation markers including serum Alb, serum Cr, serum phosphorus and Hs-CRP. Lower serum magnesium is a risk factor of CV mortality in MHD patients. Intervention studies are needed to clarify whether magnesium supplementation is beneficial for improving patient prognosis, when MHD patients had inflammatory and malnutrition.

Lower Hydrogen Sulfide Is Associated with Cardiovascular Mortality, Which Involves cPKCßII/Akt Pathway in Chronic Hemodialysis Patients.

BACKGROUND/AIMS: To evaluate the relationship between plasma hydrogen sulfide (H2S) and cardiovascular risk markers, including pulse pressure (PP), left ventricular mass index (LVMI) and intima-media thickness (IMT), and mortality in chronic hemodialysis (CHD) patients and further investigate the underlying cardiovascular protection mechanism of H2S. METHODS: CHD patients, 113 of them, were studied. Plasma H2S was measured through zinc acetate reaction. cPKCßII membrane translocation and phosphorylation of Akt were detected by western blot. RESULTS: Lower plasma H2S level in CHD patients was predictor of an increased PP, LVMI and IMT. Patients with lower H2S had a lower survival at the end of the study. H2S was an independent predictor of all-cause and cardiovascular mortality when adjusted for other risk factors. CHD patients with lower H2S showed an increase of cPKCßII activation, but phosphorylation of Akt decreased. The level of VCAM-1 and ICAM-1 increased significantly. CONCLUSIONS: Lower plasma H2S in CHD patients is associated with cardiovascular risk factors and mortality, which may be mediated by the cPKCßII/Akt pathway and further VCAM-1/ICAM-1 upregulation.

Serum hepcidin predicts uremic accelerated atherosclerosis in chronic hemodialysis patients with diabetic nephropathy.

BACKGROUND: Hepcidin, as a regulator of body iron stores, has been recently discovered to play a critical role in the pathogenesis of anemia of chronic disease. Atherosclerotic cardiovascular disease is the most common complication and the leading cause of death in chronic hemodialysis (CHD) patients. In the current study, we aimed to explore the relationship between serum hepcidin and uremic accelerated atherosclerosis (UAAS) in CHD patients with diabetic nephropathy (CHD/DN). METHODS: A total of 78 CHD/DN and 86 chronic hemodialyzed nondiabetic patients with chronic glomerulonephritis (CHD/non-DN) were recruited in this study. The level of serum hepcidin-25 was specifically measured by liquid chromatography-tandem mass spectrometry. Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. RESULTS: High serum level of hepcidin-25 was seen in CHD patients. Serum hepcidin-25 in CHD/DN was significantly higher than that in CHD/non-DN patients. Serum hepcidin-25 was positively correlated with ferritin, high-sensitivity C-reactive protein (hs-CRP), TNF-α, and IL-6 in CHD/DN patients. CHD/DN patients exhibited higher common carotid artery intima media thickness (CCA-IMT), hs-CRP, and hepcidin-25 levels than that in CHD/non-DN patients. Moreover, in CHD/DN patients, CCA-IMT was positively correlated with serum hepcidin, hs-CRP, and low-density lipoprotein-cholesterol. On multiple regression analysis, serum hepcidin and hs-CRP level exhibited independent association with IMT in CHD/DN patients. CONCLUSIONS: These findings suggest possible linkage between iron metabolism and hepcidin modulation abnormalities that may contribute to the development of UAAS in CHD/DN patients.

Correlation of Lower Concentrations of Hydrogen Sulfide with Activation of Protein Kinase CßII in Uremic Accelerated Atherosclerosis Patients.

BACKGROUND: Hydrogen sulfide (H 2 S) plays a protective role in chronic hemodialysis (CHD) patients. In this study, we further investigate the relationship between H 2 S and conventional protein kinase CßII (cPKCßII) in CHD patients with uremic accelerated atherosclerosis (UAAS). METHODS: A total of 30 healthy people, 30 CHD patients without AS and 30 CHD patients with AS (CHD + AS) were studied. Plasma H 2 S was measured with a sulfide sensitive electrode, and cPKCßII membrane translocation was detected by Western blotting. RESULTS: Plasma H 2 S in CHD + AS group was significantly lower than that in CHD patients. cPKCßII membrane translocation in CHD + AS group increased significantly compared with CHD group. Plasma H 2 S concentration was negatively correlated with cPKCßII membrane translocation in CHD + AS patients. CONCLUSIONS: These findings suggest a possible linkage between H 2 S metabolism and cPKCßII activation, which may contribute to the development of UAAS in CHD patients.

[Pharmacokinetic effect of combined administration on spinosin and ferulic acid in monarch drug Ziziphi Spinosae Semen kernel].

To study the pharmacokinetic effect of different combined administration with monarch drug Ziziphi Spinosae Semen on its main components in rats. Sprague-Dawley (SD) rats were randomly divided into Ziziphi Spinosae Semen group, Ziziphi Spinosae Semen-Fructus Schisandrae Chinensis group, Ziziphi spinosae Semen-Salviae Miltiorrhize Radix et Rhizoma group and Zaoren Ansheng prescription group. After oral administration, HPLC was eluted with the mobile phase of acetonitrle-0.03% phosphate acid water in a gradient mode. The detection wavelength was 280 nm. The pharmacokinetic parameters of spinosin and ferulic acid were calculated by DAS 2. 0 software. Compared with Ziziphi Spinosae Semen group, Ziziphi Spinosae Semen-Fructus Schisandrae Chinensis group, Ziziphi Spinosae Semen-Salviae miltiorrhizae Radix et Rhizoma group showed a lower maximum plasma concentration (C(max)) and area under curve (AUC(0-t)) for spinosin and ferulic acid but higher clearance speed (CL/F); whereas the Zaoren Ansheng prescription group showed higher maximum plasma concentration (C(max)) and area under curve (AUC(0-t)) for spinosin and ferulic acid but lower clearance speed (CL/F). Compared with Ziziphi Spinosae Semen group, prescription group showed slower metabolism of spinosin and ferulic

Correlation of lower concentrations of hydrogen sulfide with atherosclerosis in chronic hemodialysis patients with diabetic nephropathy.

BACKGROUND/AIMS: To explore the relationship between hydrogen sulfide (H2S) and uremic accelerated atherosclerosis (UAAS) in chronic hemodialysis patients with diabetic nephropathy (CHD/DN). METHODS: A total of 36 CHD/DN and 32 chronic hemodialyzed non-diabetic patients with chronic glomerulonephritis (CHD/non-DN) were studied. Plasma H2S was measured with a sulfide sensitive electrode. RESULTS: Plasma H2S in CHD/DN was significantly lower than that in CHD/non-DN patients. Plasma H2S was positively correlated with plasma TGF-ß1, and negatively correlated with MMP-12 in CHD/DN patients. CHD/DN patients exhibited higher CCA-IMT, hsCRP, and lower H2S levels than in CHD/non-DN patients. Moreover, in CHD/DN patients, CCA-IMT was negatively correlated with plasma H2S, and positively correlated with hsCRP and LDL. On multiple regression analysis, H2S levels exhibited independent association with IMT in CHD/DN patients. CONCLUSIONS: These findings suggest possible linkage between H2S metabolism and TGF-ß/Smad signaling pathway modulation abnormalities that may contribute to the development of UAAS in CHD/DN patients.

[Pharmacokinetic effect of Sappan Lignum on hydroxysafflor yellow A in Carthami Flos].

OBJECTIVE: To investigate the pharmacokinetic effect of Sappan Lignum on hydroxysafflor yellow A (HSYA) in Carthami Flos. METHOD: Concentration of HSYA in rat plasma was detected by RP-HPLC after rats were orally administered with extracts of Carthami Flos or Carthami Flos combined with Sappan Lignum. Pharmacokinetic parameters were calculated by DAS 2.0 pharmacokinetic software. RESULT: In vivo pharmacokinetic models of HSYA were two-compartment open models in both of the Carthami Flos group and the Carthami Flos combined with Sappan Lignum group. After compatibility, HSYA showed a significant lower in apparent volumes of distribution of t(1/2Ka), t(1/2alpha) and V1/F, with slight advance in T(max). CONCLUSION: Sappan Lignum can accelerate absorption, distribution and metabolic process of HSYA in vivo and reduce its accumulation in vivo.

[Serum level of 25(OH)D and its relevant influencing factors in patients on maintenance hemodialysis].

OBJECTIVE: To explore the serum level of 25(OH)D and its relevant influencing factors in patients on maintenance hemodialysis. METHODS: The serum level of 25(OH)D was detected by electrochemiluminescence. A total of 162 patients on maintenance hemodialysis were divided into 3 groups according to the serum level of 25(OH)D: vitamin D deficiency: 25(OH)D ≤ 15 µg/L, vitamin D insufficiency: 25(OH)D ≤ 30 µg/L and vitamin D normal: 25(OH)D > 30 µg/L. Age, gender, relevant biochemical indices, high sensitivity C-reactive protein (hsCRP) and HOMA-IR were compared among there groups. The associations between 25(OH)D and the influencing factors of its levels were analyzed by Pearson's correlation. The independent factors correlated with the level of 25(OH)D were estimated by multiple linear regression. RESULTS: The average level of 25(OH)D was 10.3 (range: 4.0 - 43.5) µg/L and the prevalence of 25(OH)D insufficiency and deficiency 88.9% (144/162). Significant differences existed in age, cholesterol (CHOL), low density lipoprotein (LDL), lipoprotein(a) (LP(a)), creatinine (Cr), lg(hsCRP), lg(reductase inhibitor) (lg(RI)) and lg(vitamin D) (lg(VitD)) between three groups (all P < 0.05). Pearson's correlation analyses revealed that the serum levels of albumin (ALB), Cr and Ca(2+) were correlated positively with lg(VitD) while those of white blood cell, CHOL, LDL, Lp(a), age, RI and hsCRP were correlated negatively with VitD. Multiple linear regression analyses demonstrated that hsCRP, RI, LDL and age were the independent influencing factors of the serum levels of 25(OH)D. CONCLUSIONS: The prevalence of 25(OH)D insufficiency and deficiency is high. And microinflammation and insulin resistance are closely correlated with the insufficiency and deficiency of 25(OH)D. The independent influencing factors of serum 25(OH)D are hsCRP, RI, LDL and age.

Isopropyl 3,4,5-trihy-droxy-benzoate.

In the title compound, C(10)H(12)O(5), the dihedral angle between the benzene ring is almost coplanar with the attached C(O)-O-C group [dihedral angle = 0.32 (15)°]. In the crystal, two intermolecular O-H⋯O hydrogen bonds make R(4) (4)(26) ring mofits.

Isopropyl 3,4-dihy-droxy-benzoate.

In the crystal structure of the title compound, C(10)H(12)O(4), O-H⋯O hydrogen bonds incorporating R(2) (2)(10) and R(2) (2)(14) motifs link mol-ecules into chains along [1[Formula: see text]0]. An intra-molecular O-H⋯O hydrogen bond is also observed.

Improvement of hypertension and LVH in maintenance hemodialysis patients treated with sustained-release isosorbide mononitrate.

BACKGROUND: Hypertension and left ventricular hypertrophy (LVH) are independent predictors of morbidity and mortality in maintenance hemodialysis (MHD) patients. The level of serum asymmetric dimethylarginine (ADMA) is increased in MHD patients, which is a kind of uremic toxin. It can competitively inhibit nitric oxide production from L-arginine, which can increase vascular resistance, then lead to endothelium dysfunction, hypertension, LVH and decrease of ejection fraction. A sustained-release preparation of isosorbide mononitrate can lead to vasodilatation by releasing nitrogen monoxide. But it remains unclear whether oral isosorbide mononitrate in MHD patients can control blood pressure (BP) and reverse LVH. The aim of the present study was to evaluate the safety and efficacy of oral sustained-release isosorbide mononitrate on hypertension and LVH in MHD patients. METHODS: One hundred and forty-four MHD patients with hypertension were enrolled in this perspective, randomized, controlled, single-center trial. All patients accepted antihypertensive drugs at baseline, including renin-angiotensin system inhibitor, calcium channel blocker, ß-receptor blocker or a-receptor blocker. Seventy-two patients (nitrate group) took isosorbide mononitrate 30 mg daily, titered to a maximal dosage of 120 mg daily for 24 weeks. The dosage was adjusted once a week according to BP. The remaining 72 patients (non-nitrate group) did not take nitrate drugs other than antihypertensive drugs. BP, left ventricular mass index (LVMI), heart rate, interdialytic weight gain (IDWG) and hemoglobin (Hb) were monitored. RESULTS: After 4, 8, 12 and 24 weeks of treatment, BP levels decreased in both nitrate and non-nitrate groups. BP in the nitrate group was significantly lower than in the non-nitrate group. But there was no statistical significance in the levels of response rate and control rate of BP between the 2 groups (response rate of BP: 91.4% vs. 86.1%, X2=1.004, p=0.316; control rate of BP: 60.0% vs. 47.2%, X2=2.230, p=0.127). BP before hemodialysis was maintained between 12 and 24 weeks in the nitrate group despite the decrease in total daily category and quantity of hypotensive drugs. At week 24 of treatment, LVMI in the nitrate group was significantly decreased from 65.3 ± 14.2 g/m2.7 to 51.2 ± 10.0 g/m2.7, and that in the non-nitrate group was also significantly decreased from 63.7 ± 16.7 g/m2.7 to 56.1 ± 13.8 g/m2.7. But LVMI in the nitrate group was significantly lower than that in the non-nitrate group. The prevalence of LVH in the nitrate and non-nitrate groups decreased 17.2% and 9.8%, respectively. There was a significant difference in both groups at 24 weeks (X2=4.480, p=0.034). During 24 weeks of follow-up, the incidence of acute left heart failure in the nitrate group was 1.4% (1/70), which was significantly lower than in the non-nitrate group (11.1%, 8/72; X2=5.605, p=0.033). The incidence of adverse events was 1.4%. CONCLUSIONS: Sustained-release isosorbide mononitrate, which is safe and well tolerated, can effectively control BP, decrease the category and quantity of hypotensive drugs, improve left ventricular hypertrophy and reduce the incidence of acute left heart failure in MHD patients.

Clinical features of 2009 pandemic influenza A (H1N1) virus infection in chronic hemodialysis patients.

BACKGROUND/AIMS: Infection is one of the most common complications and is considered the second leading cause of death in dialysis patients with end-stage renal disease. After the first cases of 2009 pandemic influenza A (H1N1) virus in China became public, persons with suspected infection and those who were in contact with persons with suspected infection were tested. Whether the presentation and clinical course of H1N1 influenza is similar in the dialysis population to the general population is currently unknown. Hemodialysis patients in whom an infection was confirmed were hospitalized and quarantined, and patients on chronic hemodialysis were closely observed for the purpose of investigating the nature and duration of the disease. METHODS: From May 2009 to February 2010, we observed 15 hemodialysis patients infected with the 2009 pandemic influenza A (H1N1) virus who were quarantined in Beijing Chao-Yang Hospital, Capital Medical University. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing was used to confirm infection, the clinical features of the disease were closely monitored. RESULTS: The mean age of the 15 patients was 47.6 years, and 9 of the 15 patients were male. The diagnoses were all made in the hospital. All of the 15 patients had fluid overload. The median incubation period of the virus in hemodialysis patients was 4 days (range: 1-7 days). The most common symptoms were dyspnea (in all of the 15 patients) and productive cough (in all of the 15 patients). One of the 15 patients had low-grade fever, and the other 14 patients were afebrile. Lymphopenia, which was common in 12 of the patients, typically occurred on day 2 (range: days 1-3) and resolved by day 9 (range: days 7-11). Hypoxemia was observed in all of the patients. Six of the 15 patients developed respiratory failure requiring mechanical ventilation on days 7-9 because they were complicated by Escherichia coli nosocomial pneumonia. All the patients were placed in respiratory isolation and were treated with oseltamivir. The median length of time during which patients had positive real-time RT-PCR test results was 12 days (range: 7-19 days), which was longer than that in general population. CONCLUSIONS: The presentation and clinical course of H1N1 influenza A in the hemodialysis patients was atypical and relatively serious, which differed from the general population in China. Furthermore, these patients may have an extended period of viral shedding.

Recurrent transient loss of consciousness induced by acute massive gastrointestinal hemorrhage during hemodialysis: a case report.

A 67-year-old man with chronic hemodialysis (HD), who had end-stage renal disease secondary to diabetic nephropathy and had been on HD for 9 years with ultrapure dialysis solution, is presented with recurrent transient loss of consciousness during HD.

Hepatitis C viral infection in a Chinese hemodialysis unit.

BACKGROUND: The prevalence of hepatitis C virus (HCV) infection among maintenance hemodialysis (MHD) patients varies among countries and among dialysis units within a single country. The present study aimed to investigate the prevalence and characteristics of HCV infection in MHD patients in a Chinese hemodialysis unit. METHODS: One hundred and ninety-two patients on MHD for an average of (86.1 ± 30.0) months (range 6 - 181 months) were enrolled in this cross-sectional study. HCV antibody and HCV-RNA were measured in these MHD patients before hemodialysis by enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods. According to the result, all the patients were then divided into two groups: Group I was positive for HCV antibody and/or HCV-RNA (n = 32), and Group II was negative for HCV antibody and HCV-RNA (n = 160). The following information was obtained for all the patients: socio-demographic data, history of blood transfusions and kidney transplantation, and some laboratory values. The MHD patients who were positive for HCV antibody and/or HCV-RNA were followed for more than three years. The disease activities were graded into "asymptomatic" if alanine aminotransferase (ALT) was less than 40 U/L, "low activities" if ALT was 40 - 79 U/L, and "high activities" if ALT was equal to or above 80 U/L. RESULTS: The prevalence of HCV infection in MHD patients in our dialysis unit in May 2009 was 16.7%, which was significantly higher than in general population (3.2%). Among the 32 MHD patients with HCV positive, 20 patients were positive for HCV antibody but negative for HCV-RNA, eight patients were positive both for HCV antibody and HCV-RNA, four patients were negative for HCV antibody but positive for HCV-RNA. Eleven patients had a history of kidney transplantation and 12 had a history of blood transfusion, which were significantly more than among the MHD patients without HCV. Thirty of the 32 MHD patients were asymptomatic. There were no significant differences in age, aspartate aminotransferase (AST), ALT, or between HCV-RNA positive group and HCV-RNA negative group. But the dialysis duration in the HCV-RNA positive group was significantly longer than that in the HCV-RNA negative group. All the 20 HCV-RNA negative patients were asymptomatic. Two of the 12 HCV-RNA positive patients had low activity. None of the 32 cases with HCV positive markers had cirrhosis. CONCLUSIONS: A high prevalence of HCV infection in MHD patients is related to blood transfusion and kidney transplantation. Occult HCV infection is present in MHD patients. Chronic hepatitis C among MHD patients is mild in disease activity, and is not progressive, perhaps due to immunological abnormalities in these patients.

(E)-Isopropyl 3-(3,4-dihy-droxy-phen-yl)acrylate.

In the title compound, C(12)H(14)O(4), a derivative of caffeic acid [(E)-3-(3,4-dihy-droxy-phen-yl)-2-propenoic acid], an intra-molecular O-H⋯O hydrogen bond forms an S(5) ring. In the crystal, inter-molecular O-H⋯O hydrogen bonds link mol-ecules into chains propagating in [110].

[Intravenous iron sucrose in maintenance dialysis patients with renal anemia: a clinical study].

OBJECTIVE: To explore the safety and efficacy of intravenous iron sucrose in maintenance dialysis and to establish the optimal administration frequency and dose. METHODS: One hundred and ninety-four patients on maintenance dialysis with the hemoglobin (Hb) level of 60 - 100 g/L and hematocrit (Hct) of 18% - 30% were randomly divided into 2 sex, age, duration of dialysis, weekly erythropoietin dosage, and hematological parameters-matched groups: intravenous iron sucrose group (n = 102) and oral medication group (n = 92). The intravenous iron sucrose group were sub-divided into 2 subgroups: (1) hemodialysis (HD) subgroup receiving intravenous iron sucrose 200 mg once a week for 4 weeks and then 100 mg once a week for a further 8 weeks, and (2) peritoneal dialysis (PD) subgroup receiving intravenous iron sucrose 200 mg once a week for 4 weeks and then 200 mg once every other week for a further 8 weeks. The oral medication group received ferrous succinate 200 mg tid for 12 weeks. The levels of serum ferritin (SF), transferrin saturation (TSAT), Hb, and Hct were examined before treatment and 4, 8, and 12 weeks after treatment. RESULTS: (1) Compared with baseline levels, the levels of Hb, Hct, SF, and TSAT significantly increased 2 weeks after treatment in the intravenous iron sucrose group, and 4 weeks after treatment in the oral medication group (all P < 0.05). (2) The Hb, Hct, SF, and TSAT levels 4, 6, 8, and 12 weeks after treatment of the 2 intravenous iron sucrose subgroups were all significantly higher than those of the oral medication group (all P < 0.05). (3) The Hb, Hct, SF, and TSAT levels 12 weeks after treatment 6, 8, and 12 weeks after treatment were not significantly different from those 4 weeks after treatment in the intravenous iron sucrose group (all P > 0.05). (4) The response rate of the intravenous iron sucrose group was 95.09%, significantly higher than that of the oral medication group (55.44%, P < 0.05). (5) The mean EPO doses 6, 8 and 12 weeks after treatment of the intravenous iron sucrose group were significantly lower than that before treatment and those of the oral medication group (all P < 0.05). (6) The Hb, Hct, SF, and TSAT levels maintained stable during the period 6, 8, and 12 weeks after treatment in the intravenous iron sucrose group despite the decrease in dose and frequency. (7) The Hb, Hct, SF, and TSAT levels were significantly higher in the intravenous PD subgroup than in the intravenous HD subgroup. (8) No adverse event was found in the intravenous iron sucrose group, and adverse gastrointestinal effects occurred in 12 patients of the oral medication group. (9) After 12 weeks, the cost of EPO + intravenous iron sucrose was significantly higher than that of EPO + ferrous succinate. CONCLUSION: Intravenous iron sucrose effectively increases the serum iron parameters and hemoglobin levels during maintenance peritoneal dialysis and is well tolerated. Infusing intravenous iron sucrose 200 mg every two weeks can maintain the serum iron parameters and hemoglobin level in maintenance peritoneal dialysis patients and n permits reduction of the required dose of EPO. However, the total cost of intravenous iron treatment is relatively high.