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Objective:To access the clinical efficacy and safety of hydroxychloroquine (HCQ) in treatment of IgA nephropathy (IgAN).Methods:The data of IgAN patients who were diagnosed by renal biopsy in the First Affiliated Hospital, College of Medicine, Zhejiang University from May 2016 to August 2020 and had been treated with HCQ for more than 6 months without other immunosuppressants were retrospectively analyzed. The efficacy and side effects were compared between groups according to the baseline urine protein/creatinine ratio (UPCR) or whether combined with renin-angiotensin-aldosterone system inhibitor (RAASi).Results:A total of 121 patients were enrolled, including 45 males (37.19%). At baseline, the median UPCR was 0.69(0.45, 1.00) g/g; the median estimated glomerular filtration rate (eGFR) was 93.46(73.14, 115.67) ml·min -1·(1.73 m 2) -1; the median serum creatinine was 80.00(61.00, 98.00) μmol/L, and the serum albumin was (44.39±3.36) g/L. After HCQ treatment, UPCR and red blood cells were significantly decreased compared with baseline (all P<0.05). Triglyceride, total cholesterol and low-density lipoprotein cholesterol were also significantly decreased during the follow-up period. Serum creatinine, eGFR, serum albumin and serum uric acid remained stable. After 6 months of follow-up, the total remission rate was 56.88%, including 15.60% of partial remission and 41.28% of complete remission; at the end of follow-up, the median follow-up time was 280.00(214.00, 411.00) days and the total remission rate was 56.20%, including 9.92% of partial remission and 46.28% of complete remission. Group analysis showed that the remission rate was 60.53% ( n=76) and 48.48% ( n=33) at 6 months (Mann-Whitney U test, Z=-2.331, P=0.020) and 57.65% ( n=85) and 52.78% ( n=36) at the end of follow-up (Mann-Whitney U test, Z=-1.673, P=0.094) between patients with baseline UPCR<1 g/g and patients with baseline UPCR≥1 g/g; and the remission rate was 66.67% ( n=30) and 53.16% ( n=79) at 6 months (Mann-Whitney U test, Z=1.062, P=0.288) and 61.29% ( n=31) and 54.44% ( n=90) at the end of follow-up (Mann-Whitney U test, Z=0.930, P=0.352) between patients with single HCQ and patients with HCQ+RAASi. For side effects, the eGFR of 2 patients decreased by more than 30% compared with baseline, 1 patient relapsed and 1 patient developed blurred vision. Conclusions:HCQ is safe and effective for the treatment of IgAN.
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Objective:To investigate the efficacy and safety of individualized rituximab rescue therapy for active lupus nephritis with acute kidney injury (AKI).Methods:The clinical data of lupus nephritis patients with AKI treated with rituximab at the Kidney Disease Center of the First Affiliated Hospital of Zhejiang University School of Medicine from April 2017 to June 2020 were collected, and the renal remission rate and adverse events after rituximab treatment were analyzed retrospectively. The Kaplan-Meier method was used to calculate the cumulative incidence of patients' remission.Results:There were 13 patients enrolled, including 8 females, and aged (35.23±15.92) years old. The urinary protein/creatinine ratio was (5.22±1.57) g/g before rituximab treatment. Four patients were on dialysis at admission, and 9 patients without dialysis had serum creatinine of (223.22±85.73) μmol/L. Eight patients were confirmed as proliferative lupus nephritis by renal biopsies, including 7 cases with crescent formation and 1 case with thrombotic microangiopathy (TMA), and the other 5 cases without renal biopsies were clinically diagnosed as TMA. The dose of rituximab was (815±516) mg (200-2 100 mg), and all the patients reached the state of peripheral blood B cells clearance (CD19 + B cell count was<5/μl). After the first treatment of rituximab, the median time to B-cell clearance was 21(15, 35) days, and 8 patients reached B-cell depletion (CD19 + B cell count was 0). The remission rate was 12/13 (two cases reached complete remission, and 10 cases reached partial remission). Three cases stopped dialysis, and 1 case (with glomerulosclerosis of 52.94%) entered maintaining dialysis. The relapse times in the maintenance remission period of 7 patients with refractory lupus nephritis declined significantly from (1.57±0.53) times in a median history of 60(20, 109) months to (0.43±0.79) times in a median history of 18(10, 23) months after the use of rituximab ( P=0.015). After using rituximab, the incidence of infection was 7/13. The median time from the use of rituximab to infection was 26(4, 44) days. Pulmonary infection (5/13) was the most common type and all infected patients recovered after anti-infection treatment. Conclusions:Rituximab can be used in the treatment of active lupus nephritis with AKI, especially in patients with crescent formation and TMA, but the infection should be paid close attention to and prevented.
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Objective:To analyze the weight score and clinical application of 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) systemic lupus erythematosus (SLE) classification criteria in lupus nephritis patients.Methods:Lupus nephritis patients with renal biopsy results who were admitted in the First Affiliated Hospital of Zhejiang University College of Medicine between January 2014 and December 2018 were enrolled retrospectively. According to whether these patients were treated with glucocorticoids and/or immunosuppressants at the time of renal biopsy, they were divided into untreated group and post-treatment group. The weight scores were compared between the two groups, and the relationship between each weight score and remission after treatment was analyzed. Taking no remission as the end event, Cox regression analysis was used to analyze the influence of each weighted integral on the end event.Results:A total of 153 patients were enrolled, including 131 (85.6%) females. These were 70 (45.8%) patients in the untreated group and 83 (54.2%) patients in the post-treatment group. The patients in the untreated group had higher scores of fever (>38.3℃), blood system involvement, low complement and positive specific antibodies than those in post-treated group (all P<0.05). In a median follow-up of 34 (6-50) months, 99 patients (64.7%) achieved complete remission, 38 patients (24.8%) achieved partial remission and 16 patients (10.5%) had no remission. With no remission as the endpoint event, univariate Cox regression analysis showed that proliferative lupus nephritis (renal score of 10 points vs 8 points) and neuropsychiatric involvement were the risk factors (both P<0.05), while multivariate Cox regression analysis showed that neuropsychiatric involvement ( HR=4.758, 95% CI 1.324-17.101, P=0.017) was an independent risk factor. Conclusion:The weight scores of 2019 EULAR/ACR SLE classification diagnostic criteria have certain predictive value for remission of patients with lupus nephritis.
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Objective:To explore the related factors of postoperative adjuvant therapy for cervical cancer stagedⅠB1-ⅡA2 [according to 2018 International Federation of Gynecology and Obstetrics (FIGO) staging standard], and to establish a nomogram model to predict the risk of postoperative adjuvant therapy for locally advanced cervical cancer.Methods:A total of 714 patients with cervical squamous cell cancer staged FIGO ⅠB1-ⅡA2 treated by surgery in Anhui Provincial Hospital were selected as the research objects from January 2009 to December 2019, and their clinicopathological data were analyzed. Multiple logistic regression analysis was used to determine the influencing factors, and a nomogram model was established to predict the risk of postoperative adjuvant treatment of cervical cancer. The predictive performance of the model was evaluated with the consistency index (C-index), and the compliance of the model was evaluated with the calibration curve.Results:Univariate analysis suggested that postoperative adjuvant therapy for cervical cancer was associated with gravidity ( χ2=11.506, P=0.001), underlying disease (hypertension or diabetes) ( χ2=7.668, P=0.006), squamous cell cancer antigen (SCC-AG) level ( χ2=19.392, P<0.001), imaging risk factors ( χ2=16.392, P<0.001), FIGO stage ( χ2=25.686, P<0.001), tumor size ( χ2=9.392, P=0.025) and surgical path ( χ2=16.590, P<0.001). Multivariate logistic regression analysis suggested that the number of pregnancy >2 times ( OR=1.951, 95% CI: 1.355-2.808, P<0.001), SCC-Ag ≥1.5 μg/L ( OR=2.021, 95% CI: 1.444-2.829, P<0.001), FIGO stage ⅠB3-ⅡA2 [ⅠB3 ( OR=1.933, 95% CI: 1.139-3.282, P=0.015); ⅡA1 ( OR=2.723, 95% CI: 1.556-4.765, P<0.001); ⅡA2 ( OR=3.159, 95% CI: 1.502-6.646, P=0.002)], with underlying disease (hypertension or diabetes) ( OR=1.867, 95% CI: 1.051-3.318, P=0.033), imaging risk factors ( OR=1.997, 95% CI: 1.127-3.537, P=0.018), without neoadjuvant therapy [preoperative neoadjuvant therapy for 1 cycle ( OR=0.402, 95% CI: 0.207-0.783, P=0.007)] and laparoscopic surgery ( OR=2.177, 95% CI: 1.524-3.112, P<0.001) were independent influencing factors for postoperative adjuvant treatment of cervical cancer. Based on the screened variables, the nomogram model to predict the risk of postoperative adjuvant treatment for cervical cancer has good predictive performance (C-index was 0.702) and compliance. Conclusion:The number of pregnancy >2 times, SCC-Ag ≥1.5 μg/L, FIGO stage ⅠB3-ⅡA2, with underlying disease (hypertension or diabetes), imaging risk factors, without neoadjuvant therapy, and laparoscopic surgery are independent influencing factors for postoperative adjuvant treatment of cervical cancer. A nomogram model has been constructed to predict the risk of postoperative adjuvant therapy for locally advanced cerrical cancer, and it can provide evidence for clinical treatment selection.
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Objective To study the renal prognosis with the type and proportion of crescentic in adult Henoch Schonlein purpura nephritis (HSPN).Methods A total of 275 HSPN cases diagnosed in the First Affiliated Hospital of Zhejiang University were retrospectively analyzed.According to the pathological results,they were divided into four groups:99 patients in none crescent group (NC),35 patients in segmental crescents group (SC),122 patients with circumferential crescent ＜25％ (C1),and 19 patients with circumferential crescent≥25％ (C2).Renal prognostic events were defined as estimated glomerular filtration rate (eGFR) decreased by 30％ over baseline within 2 years,doubling of serum creatinine or end-stage renal disease during follow-up.Kaplan-Meier survival analysis was used to compare the renal survival rate of each group.Univariate and multivariate Cox regression model was used to recognize the risk factor of poor renal outcome.Results There was no significant difference in age,extra renal organ performance and mean arterial pressure among groups.Among NC group,SC group,C1 group and C2 group,difference in serum creatinine (P=0.001),eGFR (P=0.003) and proteinuria levels (P ＜ 0.001) were statistically significant.There was no significant difference in the ratio of global sclerosis,mesangial hypercellularity and interstitial inflammation/fibrosis among the groups.The patients were followed up for 86(58,116) months.The renal survival rates of NC group,SC group,C1 group and C2 group were 96％,100％,83.6％ and 68.4％ respectively.Kaplan-meier survival analysis showed significant differences (Log Rank=23.24,P＜ 0.001).Cox multivariate regression analysis indicated that presence of circumferential crescent (HR=3.59,95％CI 1.34-9.62,P=0.008) and low eGFR (HR=0.979,95％ CI 0.968-0.989,P ＜ 0.001) were independent prognostic factors.Conclusion The presence of circumferential crescent and low eGFR level are independent risk factors for poor renal prognosis in HSPN patients.
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OBJECTIVE@#: To observe the expression of gene in the early development stage of wild zebrafish embryos.@*METHODS@#: The collinearity of gene and the sequence similarity of G6pd protein were analyzed with gene database and BLAST software, respectively. Expression of gene in different development stages of zebrafish embryos was detected by hybridization. The -EGFP-pCS recombinant plasmids were microinjected into zebrafish embryos, and fluorescence was observed under a fluorescence microscope. The expression of G6pd protein at 24, 48 and 72 hour post fertilization (hpf) zebrafish embryos was detected by Western blotting; the enzyme activity of G6pd at 24, 48 and 72 hpf zebrafish embryos was detected by modified G6pd quantitative ratio method.@*RESULTS@#: The G6pd protein similarity of zebrafish and human was 88%, and that of zebrafish and mouse was 87%. The results of hybridization showed that the gene was mainly expressed in the hematopoietic tissues of zebrafish; the results observed after microinjection of -EGFP-pCS recombinant plasmid were consistent with the results of hybridization. At 24, 48 and 72 hpf, the relative expression levels of G6pd protein in zebrafish embryos were 1.44±0.03, 1.47±0.05, and 1.54±0.02, respectively(>0.05); the G6pd enzyme activity levels were 1.74±0.17, 1.75±0.12, 1.71±0.22, respectively (>0.05).@*CONCLUSIONS@#: The study has observed the expression of gene and G6pd protein, and G6pd enzyme activity in zebrafish embryos at different development phases, which provides a reference for the establishment of a zebrafish G6PD deficiency model.
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Animals , Humans , Mice , Embryo, Nonmammalian , Gene Expression Regulation, Developmental , Glucosephosphate Dehydrogenase , Genetics , In Situ Hybridization , Plasmids , Genetics , Zebrafish , Embryology , GeneticsABSTRACT
Objective To analyze and summarize the cases of pregnancy on maintenance hemodialysis (MHD),and review the literature.Methods Seven cases of pregnancy and childbirth in patients on MHD in the First Affiliated Hospital of Zhejiang University from Jan 2009 to Dec 2017 were analyzed,and the literature about pregnancy in patients on MHD reported in Pubmed and Web of Science database was retrieved.Both maternal and fetal outcome were studied.Results There are seven pregnant MHD patients in this center,among whom six patients went through a smooth pregnancy and one patient had intra-uterine fetal death at 14 weeks of pregnancy.The six patients had preterm labor.Among six fetuses,four grew in good health and developed well,one had physical development retardation and one had heart malformation at born.In the literature,169 cases reported pregnant patients and 182 fetuses were evaluated,of which 145 live infants were delivered,79.67％ overall fetal survival rate,with gestational age of (32.94±3.34) weeks.In 164 delivered fetuses,147 were preterm labor (89.63％).The weight of live births was (1824±609) g.There were no maternal deaths.Fetal survival rate was zero in ＜ 20 weeks of gestational age,20-24 weeks was 14.29％,25-27 weeks was 45.45％,≥28 weeks was 94.44％.The fetal survival rate was higher in pregnant woman receiving hemodialysis≥28 hours weekly compared to women receiving ＜ 16 hours weekly (92.31％ vs 52.94％,P=0.02).Conclusions There are still a very high matemal and fetal complication rate in hemodialysis patients,especially in fetus.Gestational age≥28 weeks has a high fetal survival rate.Intensive dialysis during pregnancy may benefit higher fetal survival rate.
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ObjectiveTo explore the application value of high freuency two-dimensional and color Doppler ultrasonography in the detection of lower limb deep venous thrombosis.MethodsEighty-nine patients with suspicious lower limb deep venous thrombosis were enrolled and received high frequency two-dimensional and color Doppler ultrasonography examination.Vessel diameter,thrombus position,size and echo and blood flow in vessel were observed.ResultsIn 89 patients,42 cases (47.2％) had femoral-iliac vein thrombus;27 cases(30.3％ ) had vein thrombus in intramuscular of cnemis; 13 cases (14.6％) had deep venous thrombosis of the whole lower limbs; 5 cases (5.6％) had intramuscular haematoma;2 cases (2.2％)had subcutaneous soft tissue edema of cnemis.Eighty-four cases were detected having vein thrombus,2 cases (2.4％) were in both lower limbs; 57 cases (67.9％) were in single left lower limb and 25 cases(29.8％)were in single right lower limb.The ratio between thrombus in single left lower limb and in single right lower limb was 2.28:1.The diameter of popliteal vein and femoral vein in affected side limb was respectively (8.8±1.2) mm and (12.9±2.7) mm,which was significantly larger than those in normal side limb[ (5.9 ±1.5) mm and (9.2±2.1 ) mm](P＜ 0.05).ConclusionHigh frequency two-dimensional and color Doppler ultrasonography has high precision in the diagnosis of lower limb deep venous thrombosis and with certain sensibility and specificity.
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Objective To explore the value of transthoracic echocardiography in diagnosis of univentricle and analyze the sonogram typing. Methods The results of 66 patients with univentricle were reviewed retrospectively,and analayzed their typing connected with the reports in the literature. Results There were 3 ultrasonic types in 66 cases:①Type A(single left ventricle) 19 cases,single ventricle with left ventricular shape,residual cavity in front of it. ②Type B(single right ventricle) 38 cases, single ventricle with right ventricular form,and residual cavity in the rear.③Type C (solitary single-ventricle) 9 cases,there was only one ventricle. Thirty-one of them were treated surgically, 5 cases without operation had MRI or cardiac catheterization examination and the remaining 26 patients were only observed by echocardiography,the positive rate of diagnosis in type was 100%, the results were compared with cardiac catheterization or MRI examination and the operation: 1 cases of mixed type total anomalous pulmonary venous connection was misdiagnosed as heart-type total anomalous pulmonary venous drainage. But 1 case of descending aorta limitations narrow complicated patent ductus arteriosus(PDA), PDA was missed. The rest were completely correct diagnosis. Conclusions The transthoracic echocardiography can be used to evaluate types and all containing malformations of univentricle,and offers reliable information for operation.
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The phosphatase of regenerating liver(PRL)families of phosphatases,consisting of PRL-1,PRL-2,and PRL-3,are individually overexpressed in a variety of cancer cell lines and tissues when eom-pared with their normal counterparts.Several recent studies have shown that PRL-3 is expressed at a higher lev-el and at a greater frequency in colorectal cancer with liver metastases compared with primary colorectal tumorsand normal colon tissue.Expression of PRL can enhance metastatic and invasive properties of cells and initiate tumor angiogenesis in experimental mice.However,the exact mechanism and in- teracting proteins of the PRL remain unclear.With further study,PRL-3 may server as an attractive target for therapeutic intervention and marker for colon cancer metastasis.