Objective To investigate the clinical features,early diagnosis and individualized treatment of renal hypophosphatemia and osteomalacia induced by adefovir dipivoxil (ADV) in patients with chronic hepatitis B (CHB).Methods Thirty-nine CHB or hepatitis B virus (HBV)-related cirrhosis patients of renal hypophosphatemia and osteomalacia induced by ADV were consecutively collected.The clinical features were analyzed and treatment outcome was followed up.Results The mean age of the 39 patients was 54 (27-71) years old.There were 26 male and 13 female patients,and 19 patients with cirrhosis.The mean ADV treatment duration was 69 (range 18-116) months,and 31 patients were treated for 36-96 months.The mean serum phosphate was 0.68 (0.42-0.79) mmol/L.Twenty-six cases developed renal hypophosphatemic osteomaolacia,of which 14 had bone pain and 19 had abnormally elevated alkaline phosphatase (ALP).Three patients had increased serum creatinine and 24 patients had decreased estimated glomerular filtration rate (eGFR).After individualized treatment,patients gained normal serum phosphate in mean of 2.0 (range 0.5-6.0) months,and had bone pain remission in the mean of 0.8 (range 0.2-1.0) month and bone pain disappeared in the mean of 1.5 (range 0.5-5.0) months.Function indices of liver and kidney were improved gradually,and the bone mineral density examination improved slowly.Conclusions CHB and HBV-related cirrhosis patients treated with longterm ADV could develop renal hypophosphatemia and hypophosphatemic osteomalacia,which is partially reversible.Monitoring serum phosphate,creatinine and cystatin C is necessary during long-term ADV therapy.After confirmed diagnosis,withdrawal or dosage reduction of ADV,and switch to telbivudine or entecavir should be considered.Meanwhile,serum phosphate and HBV DNA level should be monitored.

Objective To evaluate the diagnostic performance of a point-of-care testing for sensitive cardiac troponin Ⅰ (POCT-cTnI) in early diagnosis of chest pain patients who had a high pretest probability of acute myocardial infarction (AMI).Methods Total of 127 patients with new-onset chest pain at the emergency department were enrolled.Blood samples were drawn for the routine blood test,and determined POCT-cTnI and central laboratory testing for high sensitive cardiac troponin T (CLT-hscTnT) at admission,three and then at six hours after admission.All patients were divided into AMI group and non-AMI group according to the final diagnosis,which was adjudicated independently by two physicians who reviewed all available medical records for the 90-day follow-up period,and they were unaware of the results of the investigational assays of cardiac troponins.The receiver operating characteristic (ROC) curves were constructed to assess and compare the diagnostic performance of AMI of two cardiac troponin assays.The comparison of areas under the ROC curves (AUC) was performed by DeLong test,and the sensitivity,specificity,negative predictive values (NPV) and positive predictive values (PPV) for the target markers were calculated by applying a maker-specific cutoff value.Results The final diagnosis of AMI was made in 40 of 127 patients (31.5 ％).The diagnostic accuracy of the two assays oBtained at presentation,as quantified by AUC,was no statistically differences (AUC for POCT-cTnⅠ,0.901,95％ CI,0.901 to 0.947;and for CLT-hscTnT,0.907,95％ CI,0.842 to 0.951;Z =0.235,P =0.745).The AUC for POCT-cTnI at 3 hours after admission was significantly higher than that on admission (0.931 vs.0.858;Z =-2.038,P =0.042),while there was on further improvement at 6 hours after admission (0.931 vs.0.949;Z =-1.435,P =0.151).With use of POCT-cTnI (cutoff value 0.023 ng/mL,which was the 99th percentile upper reference limit) on adimission,the clinical sensitivity was 77.5％,and the specificity was 94.2％.A single sample of POCT-cTnI at 3 hours after admission improved the diagnostic accuracy,with a sensitivity of 96.4％,a specificity of 92.0％,and a NPV of 98.6％,a PPV of 81.8％.While,with use of CLT-hscTnT (cutoff value 0.014 ng/mL,was the 99th percentile upper reference limit) at 3 hours after admission,the NPV reached to 100％.Conclusions The use of a POCT-cTnI assay in chest pain patients can identify and exclude the AMI rapidly and exactly at three hours after admission,and the diagnostic performance is equivalent to CLT-hscTnT.

ObjectiveTo investigate the clinical characteristics of the inpatients suffering from dengue fever in order to provide references for better diagnosis and treatment.Methods The clinical data of 158 dengue fever patients admitted to the First Affiliated Hospital of Sun Yat-Sen University from July 23rd to October 31st, 2014 during the 2014 epidemic in Guangzhou area were retrospectively analyzed, including general clinical manifestations, conventional examinations, pathogenesis, and prognosis.Results The mean age of the 158 patients was (56±20) years, with half of them over 60 years old (79 cases). Among them, 94 (59.49%) were male.① The common manifestations included fever (100%), headache (70.89%), myalgia/bone soreness (62.03%), and skin rash (54.43%). Bleeding and plasma leakage were found in 25.95% and 14.56% of the patients respectively.② Laboratory examination:leucopenia (75.32%) and thrombocytopenia (77.85%) were found, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated in 57.59% and 77.85% of the patients respectively. However, elevation of blood hematocrit was rare (1.27%).③ It was found that in the acute phase (0 - 5 days of the onset), serum dengue virus antibody IgM (DF-IgM) was positive in 63.54% of the patients (61/96), and 92.62% (113/122) of patients were dengue virus RNA (DENA-RNA) positive.④ The rate of comorbidity in this study was 55.06% (87/158), including hypertension (27.22%) and type 2 diabetes (15.82%), which were the two most common co-morbidities.⑤ All the patients were given supportive therapy to prevent complications. They were also isolated for more than 5 days after onset, and at least for 24 hours after subsidence of fever in addition.⑥ The criteria for the diagnosis of severe dengue were fulfilled in 18 patients (11.39%). One patient died of massive hemorrhage from gastro-intestinal tract, and 1 patient voluntarily left hospital with untreated multiple organ dysfunction syndrome (MODS). Another 2 patients of dengue fever died from primary cardio-cerebrovascular disease, and the remaining 154 patients (97.47%) fully recovered with supportive therapy and complication prevention measures.Conclusions The clinical manifestations of inpatients with dengue fever in this study were typical, and they manifested a higher incidence of severe illness. DENA-RNA could be a sensitive indicator for early pathogenic diagnosis. With symptomatic and supportive therapy, most patients had a good outcome. However, early diagnosis and clinical interventions of severe dengue still need further studies.

Objective:To investigate the effect of resveratrol on the expression of inflammatory cytokines and related genes in human SZ95 sebocytes induced by benzo (a) pyrene.Methods:Human SZ95 sebocytes were cultured in vitro, and divided into 4 groups: control group treated with 1‰ dimethyl sulfoxide for 27 hours, resveratrol group treated with 1 × 10 -5 mol/L resveratrol for 24 hours, benzo (a) pyrene group treated with 1 × 10 -5 mol/L benzo (a) pyrene for 3 hours, resveratrol+benzo (a) pyrene group treated with 1 × 10 -5 mol/L resveratrol for 24 hours followed by 1 × 10 -5 mol/L benzo (a) pyrene for 3 hours. Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of interleukin (IL) -1α, IL-6, aryl hydrocarbon receptor (AhR) , cytochrome P4501A1 (CYP1A1) and cytochrome P4501B1 (CYP1B1) in SZ95 sebocytes in the above groups; Western blot analysis was conducted to determine the phosphorylation level of p38 mitogen-activated protein kinase (p38 MAPK, expressed as the ratio of phosphorylated to total p38 MAPK) and AhR protein expression; enzyme-linked immunosorbent assay (ELISA) was conducted to detect levels of IL-1α and IL-6 in the cell culture supernatant in each group. One-way analysis of variance was used for comparison of means among multiple groups, and least significant difference- t test was used for multiple comparisons. Results:The mRNA and protein expression of IL-1α in SZ95 sebocytes significantly differed among the control group, resveratrol group, benzo (a) pyrene group and resveratrol+benzo (a) pyrene group (mRNA: 2.045 ± 0.272, 2.058 ± 0.154, 3.124 ± 0.094, 2.185 ± 0.337, protein: 9.132 ± 1.181, 9.429 ± 0.771, 20.361 ± 0.907, 9.917 ± 0.897, F=14.662, 101.705, P < 0.01, < 0.001, respectively) , and were significantly lower in the resveratrol+benzo (a) pyrene group than in the benzo (a) pyrene group (both P < 0.01) . In addition, the phosphorylation level of p38 was significantly higher in the benzo (a) pyrene group than in the control group, resveratrol group and resveratrol+benzo (a) pyrene group ( F=303.129, P < 0.000 1) . The mRNA expression of AhR, CYP1A1 and CYP1B1 was significantly lower in the resveratrol+benzo (a) pyrene group than in the benzo (a) pyrene group ( t=10.64, 33.599, 18.327, respectively, all P < 0.001) . The benzo (a) pyrene group showed significantly decreased protein expression of AhR compared with the resveratrol+benzo (a) pyrene group ( P < 0.001) . Conclusion:Resveratrol can inhibit the environmental pollutant benzo (a) pyrene-induced expression of inflammatory factor IL-1α in SZ95 sebocytes, which is likely mediated by the AhR and p38MAPK pathways.

Astrocytes are the most abundant cells in the central nervous system and play significant roles in normal brain. With cerebral infarction, astrocytes are activated as reactive astrocytes and form glial scars, which play an essential part in brain injury. According to their roles in neuroprotection after cerebral infarction, regulation of scar formation, nerve regeneration, maintenance of blood-brain barrier, promotion of angiogenesis and immune response, scholars have proposed a variety of therapeutic strategies based on targeting astrocytes. This article reviews the research progress on the changes in astrocyte signaling pathways before and after cerebral infarction and the related therapeutic strategies.
Astrocytes ; Cerebral Infarction ; physiopathology ; therapy ; Humans ; Neuroglia ; pathology ; Signal Transduction

BACKGROUND:As a member of bone morphogenetic proteins,growth differentiation factor-5 shows promising potential in the application of cartilage and bone repair.The affinity of growth differentiation factor-5 onto bone tissue determines protein use efficiency,so it is of great significance to prepare growth differentiation factor-5 with bone targeting capability. OBJECTIVE:To modify growth differentiation factor-5 using bisphosphonates and investigate the effects of modified protein on the growth of preosteoblasts in mice. METHODS:Pamidronate disodium/growth differentiation factor-5 complex was prepared using chemical crosslinking to couple growth differentiation factor-5 with pamidronate disodium.The functional groups and structures of the complex were characterized using Fourier transform infrared spectroscopy and circular dichromatography.To determine the bone targeting in vitro,the binding of the modified growth differentiation factor-5 with calcium phosphate and in vitro release amount of growth differentiation factor-5 were measured with an ELISA kit.Growth differentiation factor-5(control group)and the pamidronate disodium/growth differentiation factor-5 complex(experimental group)were co-cultured with preosteoblasts MC3T3-E1.Individually cultured cells were blank controls.The effect of the complex on cell proliferation and differentiation was evaluated. RESULTS AND CONCLUSION:(1)The infrared spectroscopy and circular dichromatography results indicated that the bisphosphonate/growth differentiation factor-5 complex was successfully prepared without significant changes in the protein secondary structure.In vitro protein adsorption results showed that growth differentiation factor-5 adsorption on calcium phosphate was increased by about one time after coupling with a bisphosphonate.In the presence of cysteine,growth differentiation factor-5 could be released from the bisphosphonate/growth differentiation factor-5 complex.(2)CCK-8 assay results showed that the absorbance value of the experimental group cultured for 4 and 7 days was higher than that of the control group and blank control group(P<0.000 1).After 7 days of culture,the expression of alkaline phosphatase in the experimental group was significantly higher than that in the control group and blank control group(P<0.000 1).After 13 days of culture,the content of calcium nodules in the experimental group was significantly higher than that in the control group and the blank control group(P<0.000 1).The results of qRT-PCR showed that the mRNA expression of alkaline phosphatase,osteocalcin and Runx2 in the experimental group was higher than that in the control group and the blank control group after 7 days of culture(P<0.01,P<0.001,P<0.000 1).(3)These findings exhibit that bisphosphonate modification can enhance the binding capacity of growth differentiation factor-5 to calcium phosphate as well as improve its biological activity.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and a leading cause of cancer-related death worldwide. Surgery remains the primary and most successful therapy option for the treatment of early- and mid-stage HCCs, but the high heterogeneity of HCC renders prognostic prediction challenging. The construction of relevant prognostic models helps to stratify the prognosis of surgically treated patients and guide personalized clinical decision-making, thereby improving patient survival rates. Currently, the prognostic assessment of HCC is based on several commonly used staging systems, such as Tumor-Node-Metastasis (TNM), Cancer of the Liver Italian Program (CLIP), and Barcelona Clinic Liver Cancer (BCLC). Given the insufficiency of these staging systems and the aim to improve the accuracy of prognostic prediction, researchers have incorporated further prognostic factors, such as microvascular infiltration, and proposed some new prognostic models for HCC. To provide insights into the prospects of clinical oncology research, this review describes the commonly used HCC staging systems and new models proposed in recent years.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Prognosis ; Neoplasm Staging ; Survival Rate ; Retrospective Studies