BACKGROUND:Osteoarthritis is now considered a metabolic disease.Previous studies have shown that glycolysis plays an important role in the occurrence and development of osteoarthritis.Compound 3k,as a novel small molecule inhibitor of glycolysis,has anti-inflammatory and anti-tumor effects.Therefore,it can target glycolysis and is expected to provide new ideas for the treatment of osteoarthritis. OBJECTIVE:To explore the role of Compound 3k in osteoarthritis caused by glycolytic overactivity based on the hypoxia-inducible factor 1 alpha(HIF-1α)/reactive oxygen species(ROS)pathway. METHODS:ATDC5 chondroblasts at logarithmic growth phase were taken to induce osteoarthritis in an in vitro cellular model by the action of 10 ng/mL interleukin-1β for 24 hours.The cytotoxicity of Compound 3k at different concentrations(0.25,0.5,1,2.5,5,10,15 μmol/L)was detected by cell counting kit-8 assay,and the appropriate concentrations were selected for the subsequent experiments.The chondrocytes were randomly divided into control,model and treatment groups.The model group was induced with 10 ng/mL interleukin 1β,and the treatment group was pre-stimulated with Compound 3k for 2 hours and then co-cultured with interleukin 1β.The proliferation of the cells in each group was detected by the cell counting kit-8 assay;the inflammatory level of the cells in each group was detected by the ELISA kit;the ROS,extracellular lactate and glucose contents were detected using the kit;qRT-PCR and western blot were used to detect the levels of related inflammatory factors,interleukin-6 and tumor necrosis factor-α,glycolysis-related genes glucose transporter protein-1,glyceraldehyde 3-phosphate dehydrogenase,monocarboxylate transporter protein-1 and HIF-1α. RESULTS AND CONCLUSION:Compared with the control group,the model group showed a decrease in cell proliferative activity,active glycolysis level,manifested by an increase in extracellular lactate content(P<0.001)and a decrease in glucose content(P<0.001),interleukin-6(P<0.000 1)and tumor necrosis factor-α(P<0.001).The expression levels of glycolysis-related genes glucose transporter protein-1(P<0.001),glyceraldehyde 3-phosphate dehydrogenase(P<0.001),monocarboxylic acid transporter protein-1(P<0.001)and HIF-1α(P<0.001)in the model group were all up-regulated,accompanied by oxidative stress and overproduction of ROS.Compared with the model group,Compound 3k treatment effectively increased cell proliferation activity and inhibited the level of overactive glycolysis(P<0.001),while suppressing the expression of genes related to inflammation(P<0.001)and glycolysis in osteoarthritic chondrocytes,inhibiting oxidative stress,downregulating the expression level of HIF-1α(P<0.000 1)and decreasing the content of ROS.To conclude,Compound 3k inhibits interleukin-1β induced chondrocyte inflammation,and its mechanism may be related to glycolysis and HIF-1α/ROS mediated oxidative stress.

Objective To discuss how to plot a power function graph and draw power function graphs corresponding to common quality control rules to assist medical laboratories in selecting quality control rules.Methods Commonly used quality control rules in clinical laboratory testing in China were collected,power function graphs based on the Monte Carlo method were plotted,and the simulation results with existing results were compared and tested the reliability of the method.Results The Monte Carlo method could be used to easily plot power function graphs for the most complex quality control rules such as 13s/22s/R4s/41s/8(x-).This method had a high level of accuracy,but the accuracy and precision were positively correlated with the number of simulations.In terms of statistical proportions of seven commonly used quality control rules,the 13s/22srule had the highest usage proportion,followed by the 13s/22s/R4s.The power function graph corresponding to the 13s/22s/R4s/41s/10(x-) rule was plotted,and the sigma level lines were marked to assist the laboratory in selecting quality control rules.Conclusion The Monte Carlo method accurately plotted power function graphs,and medical laboratories could use this method to independently plot efficiency function graphs to meet quality control requirements.

Objective:To evaluate the correlation between age and renal outcomes in patients with stage 2-4 chronic kidney disease (CKD) and the impact of age on CKD outcomes in kidney diseases of different etiologies.Methods:A prospective cohort study included 470 patients with stage 2-4 CKD. The Kaplan Meier method was used to analyze the differences in CKD outcomes among different age groups. The independent risk factors for CKD progression were analyzed using a multivariate Cox regression model. We adjusted for baseline differences in risk factors for CKD outcomes between two age groups using propensity score matching (PSM).Results:Among 470 patients, 39 cases of end-stage renal disease (ESRD) events (all starting dialysis) and 51 deaths were observed. The Kaplan Meier survival curve ( P=0.039) and Cox regression univariate survival analysis ( P=0.043) both showed that <60 years old is a risk factor for CKD patients to progress to ESRD. In multivariate Cox regression, age remained an independent risk factor for the progression of CKD patients (hazard ratio 0.386, 95% CI: 0.163-0.916; P=0.031). For kidney diseases with different causes, in patients with hypertensive kidney damage ( P=0.024) and primary glomerulonephritis ( P=0.047), the cumulative incidence rate of ESRD in patients <60 years old was higher than that in patients ≥60 years old. There was no statistically significant difference in all-cause mortality rates between patients aged <60 and ≥60 years old ( P=0.646). Conclusions:Elderly patients with stage 2-4 CKD have a lower ESRD risk than younger patients. This discovery helps nephrologists and decision-makers optimize the management of elderly CKD patients.

Objective:To explore the incidence, influencing factors and prognostic value of cardiac valve calcification (CVC) in chronic kidney disease (CKD) non-dialysis patients.Methods:The non-dialysis patients with CKD stage 1-5 who were hospitalized and underwent echocardiography in the Department of Nephrology, Xuanwu Hospital, Capital Medical University from January 1, 2018 to December 31, 2019 were retrospectively admitted. The patients were divided into CVC group and non-CVC group, and the clinical data were compared between the two groups. The deadline for follow-up was November 1, 2021, and the follow-up end point event was all-cause mortality. Logistic regression model was used to analyze the risk factors of CVC in patients with CKD, and Cox proportional hazards regression model was used to analyze the risk factors of all-cause mortality in patients with CKD.Results:A total of 563 patients with CKD were enrolled in the study, with age of (59.49±13.97) years old, and 352 males (62.52%). There were 325 patients (57.73%) with CKD stage 1-3 and 238 patients (42.27%) with CKD stage 4-5. The incidence of CVC in CKD stage 1-5 patients was 32.32%(182/563). Aortic valve calcification occurred in 30.73%(173/563), mitral valve calcification occurred in 9.77% (55/563), double valve (mitral and aortic valve) calcification occurred in 8.35% (47/563), and tricuspid valve calcification occurred in 0.18%(1/563). Age (t=12.223, P<0.001) and the proportions of CKD stage 4-5 ( χ 2=10.854, P=0.001), hypertension ( χ 2=7.811, P=0.005), diabetes ( χ 2=8.424, P=0.004), hyperlipidemia ( χ 2=9.331, P=0.002), and taking statins ( χ 2=4.868, P=0.027) in CVC group were significantly higher than those in non-CVC group. Total cholesterol (t=2.243, P=0.025), low density lipoprotein cholesterol (t=2.025, P=0.043), platelet count (t=2.230, P=0.026) and estimated glomerular filtration rate (t=8.630, P<0.001) in CVC group were lower than those in the non-CVC group. Logistic regression analysis results showed that age≥60 years old (≥60 years old/<60 years old, OR=7.412, 95% CI 4.514-12.170, P<0.001), CKD stage 4-5 (stage 4-5/stage 1-3, OR=2.791, 95% CI 1.730-4.505, P<0.001) and hyperlipidemia ( OR=5.241, 95% CI 3.283-8.367, P<0.001) were the independent influencing factors of CVC in patients with CKD. Five hundred and sixty-three patients were followed up for an average of 26 months, including 68 cases (12.08%) of death, 436 cases (77.44%) of survival and 59 cases (10.48%) of loss to follow-up. Multivariate Cox regression analysis results showed that age≥60 years old (≥60 years old/<60 years old, HR=2.157, 95% CI 1.127-4.127, P=0.020), serum albumin<30 g/L (<30 g/L/≥30 g/L, HR=1.923, 95% CI 1.037-3.568, P=0.038) and double valve calcification (double valve calcification/no valve calcification, HR=2.516, 95% CI 1.279-4.950, P=0.008) were the independent influencing factors of all-cause death in patients with CKD. Conclusions:CVC accounts for 32.32% in non-dialysis patients with CKD stage 1-5. Older age, worse renal function and hyperlipidemia are the independent risk factors of CVC in CKD patients. Older age, hypoproteinemia and double valve calcification are the independent risk factors of all-cause death in patients with CKD.

IgA nephropathy (IgAN) is one of the common primary glomerulonephritis, which is also an important risk factor for end-stage renal disease. Kidney transplantation is the optimal treatment for end-stage renal disease induced by IgAN, whereas there is still a risk of recurrence of IgAN after kidney transplantation. At present, research progress upon IgAN recurrence after kidney transplantation is relatively lacking. The pathogenesis of IgAN recurrence remains elusive, and its pathological manifestations are not specific. The diagnosis of IgAN recurrence still depends on renal biopsy. Besides, no effective prevention and treatment are available for recurrent IgAN. In this article, research progress on IgAN recurrence after kidney transplantation was illustrated from the perspectives of pathogenesis, diagnosis, risk factors and treatment, aiming to provide reference for clinical prevention and treatment of IgAN recurrence after kidney transplantation and improve clinical prognosis of kidney transplant recipients.

Objective:To observe the risk of acute kidney disease and disorders (AKD) in patients with coronary heart disease or non-valvular atrial fibrillation who were taking rivaroxaban for the first time in our hospital.Methods:A retrospective case-control analysis was performed using the hospital database to screen for patients with coronary heart disease or non-valvular atrial fibrillation who were taking rivaroxaban for the first time for more than 3 months during January 1, 2018 to June 30, 2019. A total of 279 patients with serum creatinine reviewed within 3 months were as the rivaroxaban group, and 317 patients with coronary heart disease or non-valvular atrial fibrillation who did not take rivaroxaban during the same period in our hospital were selected as the control group. The general condition and the incidence of AKD were compared between the two groups, and the influencing factors of AKD were analyzed by logistic regression analysis.Results:The prothrombin time and international normalized ratio were higher in the rivaroxaban group than those in the control group (both P<0.01). There was no significant difference in age, gender, serum creatinine and urea level between the two groups. The incidence of AKD in the rivaroxaban group was 4.30%(12/279), and the incidence of AKD in the control group was 1.26%(4/317). The relative risk ( RR) of the two groups of patients was 3.409. Logistic regression analysis showed that older age (≥75 years old, OR=1.166, 95% CI 1.012-1.343, P=0.033) and diabetes ( OR=34.261, 95% CI 1.639-716.326, P=0.023) were risk factors for AKD in patients taking rivaroxaban. Rivaroxaban was a risk factor for AKD in patients with coronary heart disease or non-valvular atrial fibrillation ( OR=3.500, 95% CI 1.115-10.988, P=0.032). Conclusions:The incidence of AKD in patients taking rivaroxaban for the first time due to coronary heart disease or non-valvular atrial fibrillation was 4.30%. Taking rivaroxaban is a risk factor for AKD in patients with coronary heart disease or non-valvular atrial fibrillation. Older age and diabetes are the risk factors for AKD in the rivaroxaban group.

Objective: To investigate whether metabolic syndrome (MS) independently influences the renal outcomes of chronic kidney disease (CKD) 1-4 stage patients. Methods: Since July 2006 to September 2008, a total of 766 clinically stable CKD patients in the hospital were enrolled in this prospective study and followed up until December 31th, 2016. The CKD patients were divided into MS group and non-MS group according to the Chinese Diabetes Society (CDS) criterion of MS. The renal outcomes that needs to initiate renal replacement therapy were observed and recorded during the follow-up. Kaplan-Meier analysis was used to evaluate the influence of MS on CKD patients′ renal outcomes. Cox regression analysis was used to assess the independent risk factors of renal outcome of CKD patients. Results: Among 766 patients with CKD 1-4 stage, 97 patients initiated renal replacement therapy, and the prevalence of MS was 31.5%(241/766) in CKD patients. In the CKD 1-4 stage patients, the occurring rate of initiating renal replacement therapy was significantly higher in MS group than that of non-MS group (χ²=56.367, P<0.001). Cox regression analysis showed that 24-hour urine protein ≥1.0 g, MS and initial serum phosphate ≥1.3 mmol/L were the independent risk factors of initiating renal replacement therapy in CKD 1-4 stages. Conclusions More than 1/3 CKD patients are accompanied with MS. It has been demonstrated that MS, as well as 24-hour urine protein ≥1.0 g and initial serum phosphate ≥1.3 mmol/L, are the independent influencing factors of the renal outcomes in CKD 1-4 stage patients.

Objective To investigate softening-hardness dissipating-binds effects of Fuzheng Huayu (reinforcing-healthy qi resolving-stasis)Tablet combined with anti-virus therapy on liver fibrosis, and relationship between these effects and regulation of pathway of miR-122-interleukin-10-reactive oxygen species(miR-122/IL-10/ROS).Methods The patients with chronic hepatitis and liver fibrosis(n=85)were chosen from Aug.2015 to Aug.2016,and then divided randomly into test group(n=45)and control group(n=40).The control group was treated with entecavir(0.5 mg/d)and monoammonium glycyrrhizinate(0.1 g/d),and test group, additionally with Fuzheng Huayu Tablet(4.5 g/d)for 48 weeks.After treatment,ISHAK fibrosis score was reviewed through routine pathology, and activities of serum superoxide dismutase(SOD)and ROS were detected by using ELISA.The expressions of miR-122 mRNA and IL-10 mRNA were detected by using RT-PCR, and content of serum inflammatory factors of liver fibrosis, including procollagen III N-terminal peptide(PCIIINP), type IV collagen(IV-C), hyaluronidase(HA)and laminin(LN),were detected by using immunoturbidimetry.Results ISHAK fibrosis score had no significant difference between 2 groups before treatment,and decreased in 2 groups after treatment,which was superior in test group to that in control group(P<0.05).The content of serum inflammatory factors of liver fibrosis all decreased in 2 groups after treatment,and the decreases of PCIIINP and HA were more significant in test group compared with control group(P <0.05).The activities of ROS and SOD had no difference in 2 groups before treatment,and ROS decreased in 2 groups after treatment.The inhibitory effect on ROS was better in test group than that in control group after treatment(P<0.05), and SOD increase was effectively relieved in test group after treatment(P <0.05).The expressions of miR-122 mRNA and IL-10 mRNA all decreased in 2 groups after treatment, which was more significant in test group compared with control group(P<0.05).Conclusion Fuzheng Huayu Tablet reduces directly the levels of collagen and HA, degrades abnormal deposition of extracellular matrix,and regulates dynamic balance of collagen,and it antagonizes effectively the genetic expressions of IL-10 and miR-122,relieves inflammatory disorders and controls progress of histology.

Objective · To improve the surgical procedure of correcting upper eyelid retraction.Methods · Patients suffering upper eyelid retraction of 2-5 mm caused by thyroid-associated ophthalmopathy were treated with modified levator lengthening technique in Shanghai Ninth People's Hospital (Shanghai Jiao Tong University School of Medicine,China) from July 2013 to December 2014.Results· Of the 34 patients underwent the modified levator lengthening surgery for upper eyelid retraction correction,there were 7 males and 27 females.After 6 months,upper eyelid retraction got fully resolved in 25 cases and partly improved in 9 cases.The palpebral fissure height demonstrated an average decrease of 3.7 mm (P=0.000).Patient's ocular discomfort such as photophobia and tearing were either cured or improved.Conclusion · Modified levator lengthening surgery can effectively correct upper eyelid retraction,improve the patient's appearance and cure their ocular discomfort.

Objective: To evaluate the preliminary effect for serum albumin (ALB) level in patients with chronic heart failure (CHF) treated by cardiac resynchronization (CRT).
Methods: A total of 54 CHF patients treated in our hospital from 2009-01 to 2013-12 were studied. The patients were divided into 2 groups: CRT group and Control group, in which the patients were treated by medication. n=27 in each group. The blood test of biochemistry, 24 hour dynamic ECG monitoring with QRS duration, echocardiography, ALB level, heart rate (HR), left ventricular end-diastolic dimension (LVEDD) and left ventricular ejection fraction (LVEF) were recorded at admission as baseline information, and the above examinations were repeated 2 to 3 times during 6-15 months of follow-up period.
Results: The age, gender and baseline information were similar between 2 groups. Compared with admission, during followed-up period, CRT group had increased ALB, LVEF, P<0.05, decreased HR, P<0.001, shorter QRS duration, P<0.001 and LVED remained similar;while Control group had decreased ALB, P<0.05 and LVEF, LVED, QRS duration, HR remained similar. Logistic regression analysis indicated that in CRT group, with adjusted LVEF, QRS duration and ALB, serum ALB level was the most relevant indicator for CRT efifcacy, P<0.01.
Conclusion: CRT could improve the cardiac function and increase ALB in CHF patients, therefore serum ALB level might be related to CRT efifcacy at certain degree.