Aim To investigate the effect of intestinal cholesterol absorption inhibitor Ezetimibe on lipid accumulation in RAW264.7 cells and identify the underlying mechanism.Method RAW264.7 cells were pretreated with the indicated concentrations of Ezetimibe (0,0.003,0.01 and 0.03 mol·L~(-1))for 24 hours or pretreated with the optimal concentration(0.03 mol·L~(-1))of Ezetimibe for different periods (0,6,12 and 24 h),followed by incubation with 50 mg·L~(-1) oxLDL for 24 hours,then the number of intracellular lipid droplets and lipid content were measured by using oil red O staining and HPLC; the expression of NPC1L1 was measured by Western blot.Results Pretreatment with indicated concentrations of Ezetimibe caused a concentration-dependent inhibition of intracellular lipid accumulation;pretreatment with 0.03 mol·L~(-1) Ezetimibe caused a time-dependent inhibition of intracellular lipid accumulation.It was noted that pretreatment with 0.03 mol·L~(-1) Ezetimibe for 24 hours inhibited CE by about 47%+0.1% compared with control group(oxLDL alone).Immunoblotting results showed that NPC1L1 was expressed in RAW264.7 cells and it was down-regulated after Ezetimibe treatment.Conclusions Ezetimibe causes concentration-dependent and time-dependent inhibition of lipid accumulation in RAW264.7 cells;it also reduces NPC1L1 expression in RAW264.7 cells.

ObjectiveTo investigate and compare the prevalence,awareness and risk factors of chronic kidney disease (CKD) between urban and rural population in Guangxi province in order to provide information for prevention and treatment of CKD.MethodsBy a stratified multistage random sampling method,18 to 74 years old residents in Guangxi province were surveyed. They wereevaluatedbyquestionnaire,urinaryalbumin/creatinineratio, hematuria (microscopic examination of centrifuged urine sediment),kidney B-mode ultrasound,and abnormal results were reviewed 3 months later.Estimated glomerular filtration rate(eGFR) was calculated with the simplified MDRD equation modified by a Chinese coefficient.The risk factors associated with CKD were also investigated.Results There were no significant differences between urban and rural residents in the prevalence of albuminuria (5.22％ vs 5.47％) and hematuria (1.07％ vs 1.11％)(all P＞0.05).The prevalence of renal lithiasis in rural residents was significantly higher than that in the town(10.54％ vs 6.95％)(P＜0.05).The decreased renal function between urban and rural residents(3.87％ vs 4.04％,P＞0.05) had no significant difference.The prevalence of CKD was 9.58％ in urban and 9.42％ in rural(P＞0.05).The prevalence of albuminuria according to the age distribution was different between urban and rural,which increased along with the age in urban but showed two peaks(30-40 years old and 60-74 years old) in rural.Based on logistic regression analysis,the risk factors for albuminuria were diabetes,hyperuricemia,the history of cardiovascular disease,chronic tonsillitis and HBsAg positive.The risk factors for kidney function decline were age,hyperuricemia,hypertension,diabetes,renal lithiasis and history of cardiovascular disease.The awareness rate of CKD in urban was significantly higher than that in rural (14.45％ vs 6.27％,P＜0.05).Conclusions The prevalenceof CKD has no significant difference between urban and rural in Guangxi province.The awareness rate of CKD in urban is significantly higher than that in rural.It is needed to enhance the prevention and treatment of CKD in rural.

Objective To evaluate the short-term therapeutic effects of DNA immunoadsorbent (IA) combined with glucocorticoid and immune depressant on patients with severe systemic lupus erythematosus(SLE). Methods 32 patients with severe SLE were selected to undergo DNA IA treatment combined with glucocorticoid plus cyclophosphamide therapy, and each patient received IA therapy 3 times, once 2.5 hours, with an interval of 24-48 hours to take another two times of IA. The changes in SLE disease activity index(SLEDAI)score, health status evaluation indexes〔 physiologic functional( PF) and emotional health( MH) scores〕,renal function indexes〔 blood urea nitrogen(BUN)and serum creatinine(SCr)〕 were observed; and anti-double stranded DNA antibody( ds-DNA), immunoglobulin (IgA, IgG, IgM), complements(C3 and C4)and high-sensitivity C-reactive protein (hs-CRP) were examined before and after IA treatment for 2 weeks. Results Two weeks after the combination therapy, the SLEDAI score, BUN, SCr, dsDNA, IgA, IgG, IgM, hs-CRP were significantly lower than those before treatment 〔SLEDAI score : 14.38±3.85 vs. 15.69±1.40, BUN (mmol/L): 11.22±4.78 vs. 16.31±7.90, SCr (μmol/L): 127.02±38.17 vs. 167.25±45.63, dsDNA( U/L): 1.36±0.12 vs. 1.43±0.18, IgA( g/L): 2.41±0.73 vs. 2.59±0.86, IgG( g/L): 16.82±4.83 vs. 21.01±4.84, IgM( g/L): 1.64±0.45 vs. 1.75±0.58, hs-CRP( mg/L): 14.41±2.20 vs. 14.94±2.60, P<0.05 or P<0.01〕; PF score, MH score, complement C3 were increased〔 PF score : 71.19±17.53 vs. 56.66±22.41, MH score : 74.01±15.72 vs. 61.50±17.98, C3( g/L): 0.56±0.09 vs. 0.52±0.10, all P<0.05〕; clinical symptoms were improved significantly, and no significant adverse reactions were found. Conclusion IA combined with medical treatment has shown that it has significant therapeutic effect for treatment of patients with severe SLE, and it may decrease the levels of dsDNA, IgA, IgG, IgM,hs-CRP, and increase the level of complement C3.

Objective:To evaluate the monitoring value of amplitude-integrated electroencephalography (aEEG) in brain injury among neonates with severe hyperbilirubinemia.Methods:This study retrospectively recruited 223 full-term infants with severe hyperbilirubinemia who underwent aEEG in the Department of Neonatology of Guangzhou Women and Children Medical Center from October 2018 to June 2020. Differences in serum bilirubin level and the incidence of acute bilirubin encephalopathy (ABE) between the normal group ( n=180) and abnormal aEEG group ( n=43) were compared. The monitoring value of aEEG in ABE, and its association with brain stem auditory evoked potential (BAEP) and MRI were studied. Two-independent sample t-test, Mann-Whitney U test and Chi-square test were used for comparing the differences between groups. Goodman-Kruskal Gamma was used for correlation analysis. Results:The total serum bilirubin level [(536.2±154.6) vs (422.1±103.0) μmol/L, t=-5.109, P<0.001] and the incidence of ABE [62.8% (27/43) vs 9.4% (17/180), χ2=62.366, P<0.001] in the abnormal aEEG group were significantly higher than those in the normal aEEG group. The sensitivity and specificity of aEEG in the diagnosis of ABE were 61.3% and 91.1%, respectively. With the progression of ABE from warning period to spasmodic stage, more severe voltage suppression (Gamma=0.847, P=0.003), more disordered sleep-wake cycles (Gamma=0.941, P<0.001) and a more frequent epileptic discharge (Gamma=0.976, P<0.001) were observed. Out of the 223 cases, 148 underwent BAEP. The abnormal rate of aEEG in abnormal BAEP group was significantly higher than that in normal BAEP group [32.7% (33/101) vs 6.4% (3/47), χ2=12.040, P=0.001]. The incidence of abnormal voltage in severe abnormal BAEP group was significantly higher than that in mild abnormal BAEP group [20.6% (7/34) vs 2.6% (1/38), χ2=5.858, P=0.016]. The incidence of epileptic discharge in severe abnormal BAEP group was significantly higher than that in mild abnormal BAEP group [32.4% (11/34) vs 2.6% (1/38), χ2=11.413, P=0.001] and moderate abnormal BAEP group [32.4% (11/34) vs 3.5% (1/29), χ2=8.480, P=0.004]. Among the 223 cases, 108 received MRI examination. The incidence of epileptic discharge in the cases with bilirubin brain injury image was significantly higher than those with normal MRI images [28.6% (10/35) vs 2.6% (1/39), χ2=9.864, P=0.002] and those with other abnormal images [28.6% (10/35) vs 2.9% (1/34), χ2=8.451, P=0.004]. Conclusions:aEEG monitoring is helpful in the diagnosis of ABE and can reflect disease severity. Severe hyperbilirubinemia-induced brain injury in neonates mainly manifests as increased and more frequent epileptic discharge on aEEG. There is a correlation between aEEG monitoring with BAEP and MRI findings.

At present, there is still a lack of uniform treatment strategies for hepatocellular carcinoma (HCC). Immunotherapy, especially PD-1/PD-L1 checkpoint inhibitors, is a novel therapy for HCC and can bring survival benefits to patients with advanced HCC. However, research data show that only a small number of HCC patients can benefit from this treatment regimen. To date, few biomarkers have been reported to predict the clinical effect of PD-1/PD-L1 checkpoint inhibitors in HCC patients. This article reviews the biomarkers studied for HCC and other tumors and explores the possible predictive factors for the clinical effect of PD-1/PD-L1 checkpoint inhibitors in HCC, in order to optimize the selection of treatment population and improve the clinical effect of PD-1/PD-L1 checkpoint inhibitors in the treatment of HCC.

For the quality control of cetomacrogol 1000, a gas chromatographic method for the determination of residual impurities in cetomacrogol 1000, such as ethylene oxide, 1, 4-dioxane, ethylene glycol, diethylene glycol and triethylene glycol, was established and validated.The DB-1 column with headspace injection was used to detect ethylene oxide and 1, 4-dioxane with the inlet temperature of 150 °C, the FID temperature of 250 °C, the headspace equilibration temperature of 70 °C and the equilibration time of 45 min.The VF-17MS column with liquid injection was used to detect ethylene glycol, diethylene glycol and triethylene glycol with the inlet temperature of 270 °C, and the FID temperature of 290 °C.The results showed that ethylene oxide and 1,4-dioxane have a good linearity within their specified addition amount ranges (r > 0.999), with the RSD of precision of below 8.0% and the average recovery rates of 90.6% and 101.2%; and that ethylene glycol, diethylene glycol and triethylene glycol also have a good linearity between 3 ? 60 μg/mL (r > 0.999), with the RSD of precision of below 3.0%, and the recovery rates of 96% ~ 103%.The method established in this study has good specificity, linearity, precision and recovery rate, which can effectively detect the multi-component and trace impurities.

【Objective】 To investigate the changing pattern of polymer content in the manufacturing process of human immunoglobulin, especially the correlation between pH value and polymer content, so as to provide basis for the control of polymer in human immunoglobulin products. 【Methods】 IVIG and HBIG low pH intermediate samples were taken and their pH values were adjusted to different gradients with 0.5 or 0.1 mol/L HCl. The polymer content was detected by HPLC, and the influence of different pH values on polymer content was observed and analyzed. 【Results】 With low pH value, the polymer content of samples increased from <1% to 10% with the decrease of pH value. When pH value was in the range of 3.85~3.10, the polymer content in the samples increased from 0.38% to 15.5% exponentially with the decrease of pH value. The logarithm of polymer was linearly correlated with pH value. 【Conclusion】 When pH value is low, polymer content of human immunoglobulin is significantly affected by pH value. Keeping pH value above 4.0 during the whole manufacturing process of human immunoglobulin is suggested.

This paper summarized the experience of Professor FANG Dingya in staged treatment of Sjögren's syndrome from the perspective of dryness toxin. It is believed that the cause of Sjögren's syndrome is externally-contracted dryness， consumption of essence and fluid， congenital and acquired essence deficiency， depleted essence and insufficient blood， and the core mechanism is internal accumulation of dryness toxin. The treatment can be divided into three stages， that is dryness toxin transforming into fire-heat， damp-heat and phlegm-stasis， from the perspective of dryness metal qi transformation. It is emphasized to dispel pathogen mainly， to clear and moisten with yin-nourishing medicinals in supplementation， and to treat by stages based on syndrome differentiation. For dryness toxin with fire-heat， it is suggested to moisten dryness， resolve toxins and subdue fire， with self-made Runzao Jiedu Decoction （润燥解毒汤） in modification. For dryness toxin with damp-heat， the method of nourishing yin， clearing heat and draining dampness should be used， and Chunze Decoction （春泽汤） in modification is suggested. For dryness toxin with phlegm-stasis， it is recommended to unblock collaterals， disperse phlegm and dissipate stasis， with self-made Sanyu Xiaotan Decoction （散瘀消痰汤） in modification.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.