Effect of intravitreal injection of anti-vascular endothelial growth factor agents on systemic concentration of vascular endothelial growth factor / 国际眼科杂志(Guoji Yanke Zazhi)

Chorioretinal disease has become a significant problem affecting human vision. Abnormal expression of vascular endothelial growth factor(VEGF)leads to increased fundus permeability and neovascularization. Vitreous injection of anti-VEGF agents can rapidly inhibit the level of VEGF in the eye and effectively control the development of the disease. At present, anti-VEGF agents are widely administered in ophthalmology. However, studies have shown that intravitreal anti-VEGF agents can reduce plasma VEGF concentration after entering the circulatory system, and the pointless off-target effects of drugs may lead to systemic adverse reactions. For elderly patients, patients with serious comorbidities, lactating women, premature infants and other special populations, attention should be paid to systemic VEGF inhibition after multiple injections. In this paper, in order to provide reference for clinical anti-VEGF therapy, the pharmacokinetics therapy, systemic adverse reactions, contralateral eye effects, and effects of anti-VEGF on breast milk and preterm infants were discussed, and the systemic effects of vitreous injection of anti-VEGF agents were reviewed.

Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine / 中国结合医学杂志

OBJECTIVE@#To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine.@*METHODS@#Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients.@*RESULTS@#Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD.@*CONCLUSIONS@#Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).

Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine：Membranous Nephropathy / 中国实验方剂学杂志

Traditional Chinese medicine （TCM） is a great treasure house， exhibiting unique advantages in the treatment of some difficult and critical diseases. The incidence rate of membranous nephropathy has increased year by year in recent years， and has become the first cause of primary glomerular diseases. However， its pathogenesis is not clear. Modern medicine often uses immunosuppressive therapy， but it often faces the problems of high side effects and high recurrence rate. The China Association of Chinese Medicine （CACM） invited clinical experts of TCM and western medicine to fully discuss membranous nephropathy， which was later confirmed to be one of the clinical diseases responding specifically to TCM. Apart from summarizing the pathogenesis and clinical diagnosis and treatment of membranous nephropathy in both TCM and western medicine， this paper also detailed TCM cognition， syndrome differentiation， and therapeutic schemes of membranous nephropathy， aiming to improve the clinical remission rate of membranous nephropathy and provide reference for its clinical treatment.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial / 中西医结合学报

BACKGROUND@#Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.@*OBJECTIVE@#This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m@*MAIN OUTCOME MEASURES@#The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.@*RESULTS@#A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.@*CONCLUSION@#SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.@*TRIAL REGISTRATION NUMBER@#NCT02063100 on ClinicalTrials.gov.

Type I and Ⅱ Cardiorenal Syndrome-related Biomarkers / 中国实验方剂学杂志

The physiology and pathology of the heart and kidney are interdependent and interact with each other, and dysfunction of any one of them causes dysfunction of the other, namely cardiorenal syndrome, in which type I and type Ⅱ have the highest incidence rate and are the commonest in clinic. Traditional Chinese medicine has a long history of treating the cardiorenal syndrome. It believes that the disease is located in the heart and kidney, and Wenyang Yiqi, Huoxue Lishui and other methods shall be adopted to effectively improve the heart and kidney function of patients. However,the pathogenesis of cardiorenal syndrome is complicated, and the clinical manifestations are diverse, which makes it difficult to diagnose and treat in the early stage, and causes missing of the best intervention timing and a poor prognosis. Biomarkers play a vital role in predicting the occurrence and development of cardiorenal syndrome. Therefore, efforts shall be made to look for biomarkers with better specificity and sensitivity, accurately evaluate physiological and pathological changes in heart and kidney, so as to achieve early diagnosis and early intervention of cardiorenal syndrome, and improve the effect of disease diagnosis and treatment. At present, domestic and foreign scholars have studied and applied more markers mainly in renal tubular injury, including neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 and urinary interleukin-18. In addition, other studies have found cell cycle arrest inducing factors, such as insulin-like growth factor binding protein 7, tissue inhibitor metallo proteinase-2, and fibroblast growth factor 23 associated with mineral metabolism. The increase of the content of these biomarkers in the body is earlier than the rise of serum creatinine, which can better predict the occurrence of early cardiorenal syndrome, and has a high application value and research value. After summarization of the biomarkers relating to type I and Ⅱ cardiorenal syndrome in domestic and foreign literatures, the research progress of several representative markers were reviewed to provide reference for related research.

Effects of Niaoduqing Particles () on Delaying Progression of Renal Dysfunction: A Post-trial, Open-Label, Follow-up Study / 中国结合医学杂志

OBJECTIVE@#To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction.@*METHODS@#Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period.@*RESULTS@#After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min•1.73 m, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min•1.73 m, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min•1.73 m per year.@*CONCLUSION@#Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).

mf-ERG effective evaluation of early and background diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AlM: To measure the retinal electrical activities in patients with diabetic retinopathy ( DR ) by applying multifocal electroretinogram ( mf-ERG) and evaluate the degree of visual damage at different stages of DR METHODS:Thirty cases ( 30 eyes ) aged 50 ~70 years old, excluding other diseases, were as normal group, and 99 cases ( 99 eyes ) diagnosed with type 2 diabetes were as experiment group. The cases received mf-ERG examination in the standard state, respectively. The results were statistically analyzed RESULTS: For DR patients with early and background stage, the reaction density of mf - ERG P1 wave decreased as the disease worsened, significantly reduced in non - proliferating stage and decreased more significantly in the background of the stage Ⅲ. This showed that in the macula, electrical activity had weakened before the retina without visual or morphological changes, and with the development of the disease, the electrical activity decreased more obviously. CONCLUSlON:mf-ERG can evaluate the severity of DR, especially suit in the early and background period of DR.

Effect of shenshuning recipe on the extracellular matrix accumulation of the peritoneal fibrosis rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Shenshuning Recipe (SR) on the peritoneal function, accumulation of extracellular matrix (ECM), and the expression of transforming growth factor-beta1 (TGF-beta1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the peritoneal fibrosis rats.</p><p><b>METHODS</b>The peritoneal fibrosis correlating peritoneal dialysis SD rat model was induced by injecting erythromycin and peritoneal dialysate. They were randomly divided into 4 groups according to body weight, i.e., the 1.50% peritoneal dialysate group (Group B), the 1.50% peritoneal dialysate + SR group (Group C), the 4.25% peritoneal dialysate group (Group D), and the 4.25% peritoneal dialysate +SR group (Group E), 15 in each group. Besides, another 15 rats was taken as the blank control group (n = 15, Group A). SR at the daily dose of 43.93 g/kg was given to rats in Group C and E by gastrogavage, while equal volume of normal saline was given to rats in other groups by gastrogavage. The changes of glucose in the peritoneal fluid were detected. The ultra filtration volume (UF)and mass transfer of glucose (MTG) were calculated. The pathomorphological changes of the peritoneum were observed. The distribution of collagen fiber, fibroblast count, collagen I (Col I), expressions of TIMP-1 and TGF-beta1 were determined.</p><p><b>RESULTS</b>At the end of the 6th week, statistical difference was shown in UF [(-3.3 +/- 14.2) mL] and [(-2.0 +/- 10.7) mL], MTG [(18.1 +/- 0.8) mmol/kg] and [(16.1 +/- 1.2) mmol/kg], collagen fiber [(4 721.3 +/- 541.0)%] and [(6502.7 +/- 877.4)%], fibroblast [(0.087 +/- 0.010)/mm2] and [(0.131 +/- 0.042)/mm2], Col I [(187.5 +/- 36.9)%] and [(289.7 +/- 95.6)%], TIMP-1 [(2.57 +/- 0.94)%] and [(3.63 +/- 0.29)%], and TGF-beta1 [(104.0 +/- 20.7) ng/L] and [(108.2 +/- 17.5) ng/L] between Group C and Group E, when compared with the peritoneal dialysate group at the same concentration (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>SR could postpone the development of peritoneal fibrosis in peritoneal dialysis SD rats possibly through inhibiting expressions of TGF-beta1 and TIMP-1, and hindering the over-accumulation of ECM.</p>

Preparation and characterization of mono PEGylated recombinant human interferon omega / 药学学报

The amino group PEGylation of rhIFNomega with monomethoxy polyethylene glycol succinimidyl succinate (mPEG-SS, 20 000) was investigated, and the modified mixture was separated and purified by ion exchange chromatography and gel filtration chromatography. Under the optimized purification conditions, the average content ofmono PEG-rhIFNomega in the collect liquid reached 182 microg x mL(-1). The average purified yield of mono PEG-rhIFNomega exceed to 22%, and the purity of mono PEG-rhIFNomega was greater than 98% by SDS-PAGE and RP-HPLC. Relative molecular mass of mono PEG-rhIFNomega was 43 790 detected by MALDI-TOF MS. The apparent molecular mass measured by SDS-PAGE was about 60 810. The purified PEG-rhIFNomega has the characteristics of typical PEGylated protein. Activity reservation rate of mono PEG-rhIFNomega was 15.0%, while the antigenicity decreased by at least 64 folds. In addition, the acid stability, thermal stability and stability in serum and trypsin solution of mono PEG-rhIFNomega were markedly better than those of the rhIFNomega. The pharmacological properties of mono PEG-rhIFNomega were significantly improved. The prepared PEG-rhIFNomega might be developed to a novel safe and long-acting interferon.

Effects of Shensu II Recipe on the expressions of transforming growth factor-beta1, and plasminogen activator inhibitor-1 in the focal segmental glomerulosclerosis rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effects of Shensu II Recipe on the renal function, mesangial extracellular matrix (ECM) accumulation, the expressions of transforming growth factor-beta1, (TGF-beta1), and plasminogen activator inhibitor-1 (PAI-1) in the focal segmental glomerulosclerosis (FSGS) rats.</p><p><b>METHODS</b>FSGS SD rat model was induced by injecting adriamycin. They were randomly divided into the model group, the Western medicine group, and the Chinese medicine group according to body weight. Besides, another 12 rats was taken as the blank control group. Of them, benazepril (0.33 mg/100 g) was given to rats in the Western medicine group by gastrogavage, while Shensu II Recipe (3.5 g/100 g) was given to rats in the Chinese medicine group by gastrogavage. Normal saline was given to rats in the control group and the model group by gastrogavage. Six rats died during the experiment process, among which, one in the control group, two in the model group, one in the Western medicine group, and two in the Chinese medicine group. The changes of 24 h urinary protein (24 hU, pyrogallol red method), blood urea nitrogen (BUN, urease method), serum creatinine (SCr, enzymatic assay of creatinine), serum total protein (TP, biuret colorimetry), serum albumin (ALB, bromocresol green colormetry) were detected. The pathomorphological changes of the glomerulus were observed. Fibronection (FN), collagen IV (Col IV), glomerulus sclerosis index (GSI), ECM/glomerulus area (GA), expressions of TGF-beta1, and PAI-1 were determined by semi-quantitative analysis.</p><p><b>RESULTS</b>At the end of the 12th week, improvement was shown in the Chinese medicine group (24 hU: 38.55 +/- 2.49 mg; BUN:10.87 +/- 1.78 mmol/L; SCr: 51.70 +/- 1.50 micromol/L; TP: 68.28 +/- 2.31 g/L; and ALB: 42.43 +/- 1.95 g/L). The pathomorphological observation showed that the development of glomerulosclerosis (GS) was significantly slowed down. Semi-quantitative analysis showed significant difference when compared with the model group (GSI: 1.68 +/- 0.33 grade; ECM/GA: 7.11% +/- 2.46%; FN: 4.15% +/- 1.55%; Col IV:1.47% +/- 0.48%; TGF-beta1:19.70% +/- 5.05%; PAI-1: 22.57% +/- 10.65%) ( P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>Shensu II Recipe could postpone the development of GS in FSGS rats possibly through inhibiting the expressions of TGF-beta1 and PAI-1, hindering the over-accumulation of mesangial matrix.</p>

The effect of fermentation conditions on glycosylation of recombinant human interferon omega in yeast Pichia pastoris / 生物工程学报

To investigate the influence of the fermentation conditions on glycosylation of heterologous recombinant protein in yeast Pichia pastoris, the glycosylation of recombinant human interferon omega (rhIFNomega) under various fermentation conditions, e. g., cell density, initial pH, methanol concentration, duration of the induction, and medium volume were studied. The glycosylation of rhIFNomega in the continuous fermentation process under various pH values and in batch fermentation were also investigated. In 250 mL flask, the optimal cell density, initial pH, medium volume, methanol concentration and frequency of methanol induction were 250 g/L (WCW), pH6.0, less than 30 mL, 15 g/L and 3 (in every 24 h), respectively. In the continuous process, the glycosylation of rhIFNomega could be effectively improved by maintaining the pH value at 7.0-7.5. In the batch fermentation process, the expression level of glycosylated and non-glycosylated rhIFNomega were the same, but the specified value of glycosylation/non-glycosylation was significantly lower than that in the flask culture. The reason of this phenomenon will be further studied. This research lay the foundation for the scale-up of production and the enhancement of rhIFNomega glycosylation in Pichia pastoris.