Comparative Cardiovascular Risks of Febuxostat and Allopurinol in Patients with Diabetes Mellitus and Chronic Kidney Disease.

BACKGROUND Hyperuricemia, which is common in chronic kidney disease and diabetes mellitus patients, raises health concerns. Febuxostat, a first-line urate-lowering agent, prompts cardiovascular risk questions, especially in high-risk patients. This study compared the effects of febuxostat and allopurinol on cardiovascular risk in diabetes mellitus and chronic kidney disease patients. MATERIAL AND METHODS This retrospective observational cohort study, conducted using Taiwan's National Health Insurance Research Database, focused on patients diagnosed with chronic kidney disease and diabetes between January 2012 and December 2017. The study population was divided into 2 groups: allopurinol users (n=12 901) and febuxostat users (n=2997). We performed 1: 1 propensity score matching, resulting in subgroups of 2997 patients each. The primary outcomes were assessed using a competing risk model, estimating hazard ratios (HR) for long-term outcomes, including the risks of all-cause hospitalization, hospitalization for heart failure, and hospitalization for cardiovascular interventions. RESULTS Febuxostat users, compared to allopurinol users, had higher all-cause hospitalization (HR: 1.33; 95% confidence interval [CI]: 1.25 to 1.42; P<.001), hospitalization for heart failure (HR: 1.62; 95% CI: 1.43 to 1.83; P<.001), and hospitalization for cardiovascular interventions (HR: 1.51; 95% CI: 1.32 to 1.74; P<.001). Moreover, the adverse effects of febuxostat on cardiac health were consistent across most subgroups. CONCLUSIONS Use of febuxostat in patients with diabetes mellitus and chronic kidney disease is associated with higher cardiovascular risks compared to allopurinol. Prudent evaluation is essential when recommending febuxostat for this at-risk group.

High intact fibroblast growth factor 23 levels associated with low hemoglobin levels in patients on chronic hemodialysis.

Introduction: A negative association between C-terminal fibroblast growth factor 23 (cFGF23) and hemoglobin (Hb) levels has been reported in patients with predialysis chronic kidney disease. In dialysis patients, the dominant form of serum FGF23 is intact FGF23 (iFGF23); however, its association with the Hb level remains unclear. Therefore, simultaneously monitoring iFGF23 and cFGF23 levels is crucial. In this study, we investigated the associations between both forms of FGF23 (iFGF23 and cFGF23) and renal anemia in chronic hemodialysis (CHD) patients. Methods: We included 166 CHD patients from two hospitals in this cross-sectional, observational study. The primary predictors were serum iFGF23, cFGF23, and iFGF23/cFGF23 levels. The main outcome was the Hb level. Results: Among the CHD patients included, 60.8% were men with a mean age of 59.4 ± 12.7 years. In the crude analysis, iFGF23 and iFGF23/cFGF23 levels showed a significant negative association (-0.27, p = 0.004 and -0.22, p = 0.034, respectively) with the Hb level. Even after adjusting for multiple variables (a parsimonious model), every increment of natural log transformation by 1 for (ln)iFGF23 and ln(iFGF23/cFGF23) levels showed a negative correlation with the Hb level (estimate: -0.27 [95%CI: -0.44, -0.10, p = 0.001]; -0.19 [95%CI: -0.37, -0.01, p = 0.042], respectively), whereas both were positively associated with erythropoietin-stimulating agent (ESA) hyporesponsiveness (odds ratio [OR]: [95%CI: 2.30, 1.26-4.17], p = 0.006; 1.95 [95%CI: 1.08-3.50], p = 0.025). Moreover, these abovementioned associations were more dominant in patients with diabetes who used angiotensin receptor blockers. Discussion: In conclusion, a negative association between serum iFGF23 or iFGF23/cFGF23 level and the Hb level was observed in our CHD patients. Meanwhile, a higher iFGF23 or iFGF23/cFGF23 level may predispose patients to ESA hyporesponsiveness.

[Risk Factors of Clopidogrel Resistance in the Elderly Patients with Atherosclerotic Cardiovascular Disease].

Objective To explore the risk factors of clopidogrel resistance (CR) in the elderly patients with atherosclerotic cardiovascular disease and to provide evidence for the antiplatelet therapy. Methods A total of 223 elderly patients (≥80 years old) with atherosclerotic cardiovascular disease treated in the Department of Geriatrics in the Peking University People's Hospital from January 18,2013 to November 30,2019 and meeting the inclusion criteria were enrolled in this study.The clinical data and laboratory test results were collected,including clinical disease,drug use,physical examination,complete blood cell analysis,biochemical indicators,and thromboelastogram (TEG).The rate of platelet inhibition induced by adenosine diphosphate was calculated according to the TEG.We assigned the patients into a CR group (n=84) and a control group (n=139) to analyze the incidence and influence factors of CR in the elderly patients with atherosclerotic cardiovascular disease. Results The incidence of CR was 37.7% in the elderly patients with atherosclerotic cardiovascular disease.The CR group had lower hemoglobin (t=3.533,P=0.001) and higher hypertension prevalence rate (χ2=6.581,P=0.006),proportion of multiple drugs (χ2=3.332,P=0.048),body mass index (BMI) (t=-2.181,P=0.030),total cholesterol (t=-2.264,P=0.025),triglycerides (Z=-2.937,P=0.003),low-density lipoprotein cholesterol (LDL-C) (t=-2.347,P=0.020),and proportion of women (χ2=5.562,P=0.014) than the control group.The results of multivariate Logistic regression showed that hemoglobin (OR=0.962,P<0.001),BMI (OR=1.154,P=0.003),and LDL-C (OR=1.688,P=0.018) were the factors influencing CR in the elderly patients with atherosclerotic cardiovascular disease. Conclusion Hemoglobin,BMI,and LDL-C may be independent factors associated with the occurrence of CR in the elderly patients with atherosclerotic cardiovascular disease.

Outcome Analysis of Transition From Peritoneal Dialysis to Hemodialysis: A Population-Based Study.

If a technical failure occurs during peritoneal dialysis (PD), the patients undergoing PD may be transitioned to hemodialysis (HD). However, the clinical outcomes of patients who have undergone such a transition are under studied. This study assessed whether patients undergoing HD who have transitioned from PD have the same clinical outcomes as HD-only patients. This research was a retrospective cohort study by searching a National Health Insurance research database for data on patients in Taiwan who had undergone HD between January 2006 and December 2013. The patients were divided into two groups, namely a case group in which the patients were transitioned from PD to HD and a HD-only control group, through propensity score matching at a ratio of 1:4 (n = 1,100 vs. 4,400, respectively). We used the Cox regression model to estimate the hazard ratios (HRs) for all-cause death, all-cause hospitalization, infection-related admission, and major adverse cardiac events (MACE). Those selected patients will be followed until death or the end of the study period (December, 2017), whichever occurs first. Over a mean follow-up of 3.2 years, 1,695 patients (30.8%) died, 3,825 (69.5%) required hospitalization, and 1,142 (20.8%) experienced MACE. Patients transitioning from PD had a higher risk of all-cause death (HR: 1.36; 95% CI: 1.21-1.53) than HD-only patients. However, no significant difference was noted in terms of MACE (HR: 0.91; 95% CI: 0.73-1.12), all-cause hospitalization (HR: 1.07; 95% CI: 0.96-1.18), or infection-related admission (HR: 0.97, 95% CI: 0.80-1.18) between groups. Because of the violation of the proportional hazard assumption, the piecewise-HRs showed that the risk of mortality in the case group was significant within 5 months of the transition (HR: 2.61; 95% CI: 2.04-3.35) not in other partitions of the time axis. In conclusion, patients undergoing HD who transitioned from PD had a higher risk of death than the HD-only patients, especially in the first 5 months after transition (a 161% higher risk). Therefore, more caution and monitoring may be required for patients undergoing HD who transitioned from PD.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Overexpression of CX3CR1 is associated with cellular metastasis, proliferation and survival in gastric cancer.

The CX3CR1/CX3CL1 axis is involved in the metastasis and prognosis of many types of cancer; however, whether CX3CR1 is expressed in gastric cancer cells and whether it participates in gastric cancer metastasis remain unknown. We investigated the expression of CX3CR1 in gastric cancer tissues and non­neoplastic gastric tissues in vivo and in gastric cancer cell lines and a gastric epithelial cell line in vitro, and then the functional roles of CX3CR1 in cellular metastasis, proliferation and survival were explored. We observed that CX3CR1 was highly expressed in gastric cancer tissues in vivo and was related to lymph node metastasis, higher clinical TNM stage and larger tumor size. In vitro, CX3CR1 overexpression promoted gastric cancer cell migration, invasion, proliferation and survival. Additionally, different from several chemokine receptors, CX3CR1 was also expressed in non-neoplastic gastric tissues and in gastric epithelial cells and played a functional role in vitro. Notably, gastric cancer tissues expressed higher CX3CR1 compared with that in the non-neoplastic gastric tissues in vivo, while in vitro, CX3CR1 expresssion in the gastric cancer cell lines was equivalent or significantly lower than that in the gastric epithelial cell line, which suggests that the high expression of CX3CR1 in gastric cancer in vivo might be induced, not constitutive. Altogether, our findings suggest that on the one hand overexpression of CX3CR1 promoted gastric cancer metastasis, proliferation and survival; on the other hand, appropriate expression of CX3CR1 in normal gastric tissues may play a physiological role in tissue remodeling after injury and/or epithelial renewal. Additionally, the tumor microenvironment may play an important role in the high expression of CX3CR1 in gastric cancer cells.

The intrinsic fluorescence spectrum of dilute gastric juice as a novel diagnostic tool for gastric cancer.

OBJECTIVE: To investigate the intrinsic fluorescence spectrum of gastric juice as a diagnostic method for gastric cancer. METHODS: We collected gastric juice by gastroscopy in 1,870 patients from May 2001 to March 2006, of whom 202 were involved in a preliminary test, 162 in experimental optimization and 1,506 in clinical verification. The best dilution and pH value were chosen in the experimental optimization phase. Clinical verification was based on optimized samples. Intrinsic fluorescence spectra were measured in all samples with a fluorescence spectrophotometer using an excitation wavelength of 288 nm. RESULTS: The first peak of fluorescence intensity (P(1) FI) of the intrinsic fluorescence spectrum was significantly higher in gastric juice from patients with gastric cancer than from those with benign lesions. There was no significant difference in the P(1) FI differences between patients with benign and malignant lesions with samples diluted by 20-fold to 80-fold and from pH 9 to pH 11. Clinical verification in 1,506 patients showed that P(1) FI ≥ 76.5 was the optimal cut-off on the receiver operating characteristic curve for diagnosing gastric cancers: sensitivity was 83.2%, specificity 80.7% and accuracy 82.0%. CONCLUSIONS: P(1) FI of the intrinsic fluorescence at 288 nm is significantly higher in patients with gastric cancers than in individuals with benign lesions. As a clinical indicator of gastric cancer, its sensitivity, specificity and accuracy were high.

[Effects of Helicobacter pylori, omeprazole and gastrin on the proliferation and apoptosis of gastric epithelial cell].

OBJECTIVE: to explore whether there is an interaction between Helicobacter pylori (H. pylori), omeprazole and gastrin on the proliferation and apoptosis of gastric epithelial cells. METHODS: With omeprazole, H. pylori and gastrin as treatment factors, the in vitro changes of gastric epithelial cells AGS and GES-1 were detected by MTS, Hoechst33342 and flow cytometry. RESULTS: (1) for a single factor, the gastric mucosal cells (AGS and GES-1) treated by H. pylori or omeprazole show significantly higher apoptosis than that of control group [H. pylori and 104 nmol/L omeprazole group: (17.20 ± 0.90)%, (12.81 ± 0.78)% vs (7.96 ± 1.25)%; (4.60 ± 0.34)%, (6.60 ± 0.76)% vs (3.52 ± 0.16)%; all P < 0.05]. The gastric mucosal cells treated by H. pylori or omeprazole show significantly lower proliferation than that of control group (H. pylori and 104 nmol/L omeprazole group: 13.35 ± 0.55 vs 37.78 ± 1.98, 47.62 ± 2.40 vs 62.44 ± 4.46; 27.15 ± 1.64 vs 32.76 ± 1.57, 29.42 ± 1.44 vs 48.86 ± 4.95; all P < 0.05). The differences were statistically significant and the effects were correlated with the concentration of omeprazole. Gastrin had no direct effect on cellular proliferation and apoptosis (all P > 0.05). (2) For a combinations of factors, the GES-1 cells treated with H. pylori and 500 ng/L gastrin had a significantly higher ratio [(7.25 ± 0.54)% vs (4.60 ± 0.34)%, P < 0.05], while the other groups just showed a rising trend in the proportion of apoptosis cells, but there was no statistical significance. Flow cytometry analysis showed that combinations of H. pylori, omeprazole and gastrin caused lower proliferation than that of H. pylori group, and all changes were statistically significant (AGS: 12.68 ± 0.09, 12.28 ± 0.31 vs 13.35 ± 0.55; GES-1: 22.06 ± 1.61, 18.59 ± 0.09 vs 27.15 ± 1.64; all P < 0.05). And combinations of 104 nmol/L omeprazole and 500 ng/L gastrin caused lower proliferation than that of 104 nmol/L omeprazole group (33.23 ± 5.98 vs 47.62 ± 2.40 and 25.97 ± 0.74 vs 29.42 ± 1.44, both P < 0.05). (3) When comparing the apoptosis and proliferation changes of two cell lines, gastric cancer cells AGS had a more marked changes than immortalized cells GES-1. CONCLUSION: gastrin significantly enhances the effects of omeprazole and H. pylori on gastric epithelial cells. It is speculated that the factors of omeprazole, H. pylori and gastrin may have a synergistic effect of decreased proliferation and increased apoptosis of gastric mucosal cells. Thus a long-term proton pump inhibitor treatment of H. pylori patients may carry a higher risk of atrophic gastritis. But it needs to be confirmed by further experiments.

Correlation between elevated FOXP3 expression and increased lymph node metastasis of gastric cancer.

BACKGROUND: FOXP3 was thought to express in the T-cell lineage exclusively until recently when FOXP3 was shown to be expressed by cancer cells. It was indicated that FOXP3 may play a wider role in biology by endowing tumor cells with immune suppressive activity. However, researches between FOXP3 and lymph node metastasis of gastric cancer were relatively infrequent, so the present work was aimed to investigate the relationship between FOXP3 expression and lymph node metastasis in human gastric cancer. METHODS: A total of 122 gastric cancer patients were enrolled in this study, and gastric tumor specimens and lymph nodes were acquired. Thirty patients who had chronic superficial gastritis diagnosed by gastroscopy contemporaneously in the Peking University People's Hospital were chosen randomly as the control group. Immunohistochemistry was performed to evaluate FOXP3 expression. A survival analysis on the 122 patients was then performed. Then, NCI-N87 cell lines were used to confirm FOXP3 expression in gastric carcinoma cells. Finally, evaluation of FOXP3 expression in gastric tumor and peritumor tissues in 12 patients were conducted using immunohistochemistry and Western blotting. A χ(2) test or Fisher's exact test (bilateral) was conducted to compare the percentage of positive percentage staining between groups. Kaplan-Meier analysis was performed for survival analysis. RESULTS: FOXP3 was expressed by gastric cancer cells and peritumor epithelial cells. FOXP3 expression was increased in primary tumors (58.2%) than that in control group (26.7%). In the lymph-node metastasis group, the incidence of lymph node metastasis which was less than 60% had a significant upregulation of FOXP3 in primary tumors and lymph nodes. However, the frequency of FOXP3 expression had no relationship with survival. CONCLUSION: FOXP3 probably has a relationship with lymph node metastasis of gastric cancer.

Portal vein thrombosis.

BACKGROUND: Most physicians in China may neglect portal vein thrombosis (PVT) in clinical practice. In fact, portal vein thrombosis is an important cause of non-cirrhotic portal hypertension. As the diversity of its clinical manifestations, misdiagnosis is common if we donot bear PVT in mind during differential diagnosis. Therefore, we systematically reviewed PVT in terms of etiology, pathophysiology, pathology, clinical manifestations, and management. DATA SOURCES: An English language literature search (from 1980 to 2004) was performed using Medline and Medscape, and articles closely related to PVT were selected. RESULTS: PVT is the second cause of portal hypertension after liver cirrhosis in western countries. Liver cirrhosis and hepatocellular carcinoma, intra-abdominal infection, thrombophilic disorders including myeloproliferative diseases are strongly associated with the development of PVT. Liver transplantation is an emerging etiological factor of PVT with the development and wide use of this technique. Gastrointestinal bleeding resulted from esophageal varices, abdominal pain, splenomegaly and hypersplenism and ascites are common manifestations of PVT. However there are differences in etiological and clinical presentations between children and adults. Diagnosis of PVT depends on imaging studies including Doppler ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and portography. Endoscopic therapy is recommended for variceal bleeding in PVT. Anticoagulant treatment for acute PVT is widely accepted in western countries. CONCLUSIONS: PVT may be unrecognized as the clinical manifestations are unspecific. Misdiagnosis and delayed treatment can lead to poor prognosis. Systematical collection of epidemiological and clinical data about PVT is necessary in China.

Type IV congenital choledochal cyst concurrent with acute pancreatitis: a case report.

BACKGROUND: Congenital choledochal cyst is a rare kind of bile duct deformity, resulting from cystic or shuttle-like dilation of part of the choledochal duct congenitally. We present a 20-year-old girl with a congenital choledochal cyst complicated by acute pancreatitis. METHOD: The clinical data of the woman with a congenital choledochal cyst concurrent with acute pancreatitis were retrospectively analyzed. RESULT: The congenital choledochal cyst of the woman was type IV complicated by acute pancreatitis. CONCLUSIONS: The diagnosis of congenital choledochal cyst mainly depends on CT, MRCP, and ERCP. Total excision of the choledochal cyst with Roux-en-Y hepaticojejunostomy is recommended as the treatment. For patients with type V cysts with frequently recurrent cholangitis resulting biliary liver cirrhosis, liver transplantation should be considered.

Non-alcoholic fatty liver disease: the problems we are facing.

OBJECTIVE: To review the current state of research in non-alcoholic fatty liver disease (NAFLD). DATA RESOURCES: Searching Medline (1994-2002) and Chinese Medical Journals Index (1998- 2002) for articles on NAFLD. RESULTS: NAFLD is a new and challenging field with increasing recognition although its pathogenesis is poorly understood. "Two hits" hypothesis is still the leading theory guiding current research. CONCLUSIONS: Genetic study is a promising way that might lead to breakthrough in NAFLD research. NAFLD study in China is at an initial stage and there is a long way to go.