Objective To investigate the role of increased microRNA-21 (miR-21) in the development of renal tubulointerstitial fibrosis secondary to aristolochic acid induced acute kidney injury.Methods C57BL/6J male mice were intraperitoneally injected with aristolochic acid at a dose of 10 mg/kg.Blood samples and kidneys were harvested at day 1,3,7,14,28 after aristolochic acid treatment.To assess the role of miR-21 in aristolochic acid induced acute kidney injury to chronic kidney disease progression,mice were intravenously injected with anti-miR-21 or anti-scramble (10 mg/kg) at 1 h before aristolochic acid dosing,as well as d5 and d10 after aristolochic acid dosing.Results Increased serum creatinine and severe kidney injury were found at d3 after aristolochic acid treatment.Renal tubulointerstitial fibrosis was developed at d14 after aristolochic acid treatment.Protein expression of α-SMA,vimentin and collagen Ⅰ were significantly up-regulated at d7 and peaked at d14 (P ＜ 0.01),while protein abundance of E-Cadherin decreased at d14 and lasted until d28 (P ＜ 0.01).The abundance of miR-21 increased at d7 after aristolochic acid dosing,peaking at d14 and thereafter maintaining at a high level.Anti-miR-21 intervention relieved renal injury with reduced serum creatinine (P ＜ 0.05) and attenuation of renal tubulointerstitial fibrosis.Besides,the protein expression of α-SMA,vimentin,and collagen Ⅰ/Ⅳ was all down-regulated after anti-miR-21 treatment (P ＜ 0.05).PTEN was up-regulated and the ratio of its downstream genes p-AKT/AKT was decreased.(P ＜ 0.05) Conclusions A single high dose of aristolochic acid leads to acute kidney injury and the development of renal tubulointerstitial fibrosis secondary to AKI.Renal tubulointerstitial fibrosis could be partially reversed by inhibiting miR-21 via PTEN/p-AKT pathway.

Background:Erythrocytosis,a rare paraneoplastic syndrome,generally occurs in patients with clear cell renal cell carcinoma and has never been reported in patients with chromophobe renal cell carcinoma.Case presentation:We report a case of a young man suffering from a giant (22-cm) mass on his left kidney.Because of a history of polycythemia vera,the patient had been treated for the condition for 9 years.Radical nephrectomy was successfully performed,and the postoperative pathologic examination confirmed a diagnosis ofchromophobe renal cell carcinoma.Unexpectedly,the symptom of erythrocytosis disappeared after the surgery.Further examination and analysis were performed,and we finally attributed his erythrocytosis to chromophobe renal cell carcinoma.Conclusions:Chromophobe renal cell carcinoma could cause erythrocytosis,but the clear-cut mechanism needs further research.Secondary erythrocytosis such as those related with renal tumors should be taken into consideration during the diagnosis of polycythemia vera.

Objective To discuss the necessity of closing the peritoneum during the operation of ileal conduit after the radical cystectomy.Methods We retrospectively analyzed the clinical data of 395 patients with bladder cancer who received radical cystectomy from Jan.2014 to Sep.2016.The amount of male was 327,female was 68.The mean age was (65.8 ± 9.7) years old.Patients were divided into four groups according to the surgical method of cystectomy and urinary diversion.In group A,patients,including 78 males and 9 females,were received open radical cysectomy (ORC) with extraperitoneal ileal conduit.The mean age was (67.8 ± 9.2) years old.In the preoperative clinical staging,66 cases were less than T2 and 21 cases were more than T2.Preoperative pathological grade in 83 cases and low grade in 4 cases.In group B,patients,including 31 males and 2 females,were accepted ORC with ileal conduit without peritoneum closure.The mean age was (67.3 ± 8.7) years old.Preoperative clinical staging showed less than T2 in 25 cases,more than T2 in 8 cases,The preoperative pathological grade showed high grade in 33 cases.In group C,patients,including 112 males and 27 females,were accpeted LRC with ileal conduit without peritoneum closure.The mean age was (64.3 ± 10.5)years old.The preoperative clinical staging showed less than T2 in 107 cases and more than T2 in 32 cases.The preoperative pathological grade showed high grade in 135 cases and low grade in 4 cases.In group D,patients,including 106 males and 30 females,were accepted RARC with ileal conduit without peritoneum closure.The mean age was (65.9 ±10.0)years old.Preoperative clinical staging showed less than T2 in 103 cases and more than T2 in 33 cases.The preoperative pathological grade showed high grade in 132 cases and low grade in 4 cases.Ileal conduit without peritoneum closure means completely open the peritoneum after anastomosis of the ureter and intestine in the urinary diversion surgery without shutting down the peritoneum,which is different from the extraperitoneal ileal conduit.The operating time,blood loss,blood transfusion rate,recovery time of intestinal function and perioperative complications and rate of hydronephrosis were analyzed.Results The 395 cases completed operation successfully,no LRC or RARC had been converted to ORC.The operative time was (280.1 ± 92.3) min,(233.6 ± 99.4) min,(304.8 ± 108.9) min,(364.6 ± 86.4) min in four groups,respectively (P ＜ 0.05).The blood loss in four groups were (489.1 ± 285.6) ml,(431.8 ± 233.1) ml,(373.0 ±213.7) ml,(205.6 ± 137.8) ml,respectively (P ＜0.05).The transfusion rate in four groups were 18 (20.7％),16 (48.0％),15 (10.8％),14 (10.3％),respectively (P ＜ 0.05).The mean time to flatus in four groups were (3.7 ±1.8)d,(3.6±1.0)d,(3.5±1.2)d,(2.2±1.7)d,respectively (P ＜ 0.05).While ileal obstruction rate had no statistical difference in four groups [group A 17 cases(19.5％),group B 6 cases(18.2％),group C 27 cases(19.4％),group D 19 cases(14.0％),P =0.678].Urine leakage,intestinal leakage,lymphocyst were only occurred in group A [7 cases (8.0％),2 cases (2.3％),2 cases (2.3％)].Pyelonephritis was noticed in each group,including 14 cases(16.1％)in group A,2 cases(6.1％)in group B,9 cases (6.5％)in group C,6 cases(4.4％)in group D (P ＜ 0.05).Hydronephrosis 6 months after surgery was observed in four groups,including 15 cases(17.2％)in group A,3 cases(9.1％)in group B,7 cases(5.0％)in group C,5 cases(3.7％)in group D (P ＜ 0.05).Conclusions Ileal conduit without peritoneum closure would not increase the incidence of complications,on the contrary,it would relieve the tension of anastomosis,and reduce the occurrence of complications such as urine leakage.

Colorectal cancer is one of the most common malignant tumors. Myeloperoxidase (MPO), as an oxidase in neutrophils lysosomes, plays an important role in activating carcinogenic gene intermediates and enhancing exogenous carcinogenesis. It can stimulate oxidative stress reaction in vivo by producing hypochlorite, reactive oxygen species and other oxidants, and induce gene instability factors such as DNA damage, mutation, mismatch repair and so on, which leads to the occurrence and development of colorectal cancer. MPO single nucleotide polymorphism (SNP) is related to the genetic susceptibility of cancer. Mpors 2333227-463G>A can reduce the risk of colorectal cancer. Therefore, the research on MPO, MPO-463G>A will provide new ideas and strong evidence for early detection, prevention, disease assessment and targeted treatment of colorectal cancer.

Objective:To investigate the role and probable mechanism of moderate activation of hypoxia‐inducible factor(HIF) in slowing chronic kidney disease progression of remnant kidney .Methods :Rat models of remnant kidney were established by 5/6 subtotal nephrectomy in male Sprague‐Dawley rats . And then they were randomly allocated to L‐mimosine (L‐Mim ) treatment group ,in which the rats were treated with intraperitoneal injections of L‐Mim during 5‐12 week after operation ,and untreated remnant kidney group .Meanwhile ,sham operated rats were set as control group .All rats were sacrificed at the end of week 12 ,and the specimens were collected .Results:The serum creatinine level in L‐Mim treatment group was lower than that in untreated remnant kidney group(82 .4 ± 6 .3 vs .130 .1 ± 24 .1 μmol/L ,P<0 .05) ,as well as the 24 h Ualb level (0 .7 ± 0 .1 vs .1 .7 ± 0 .5 g/d , P< 0 .05) .And the pathological changes in in L‐Mim treatment group was slightly improved while compared to untreated remnant kidney group .The result of miRNA microarray analysis showed that miR‐29c in renal cortex was up‐regulated in L‐Mim group compared with untreated remnant group and meanwhile the expressions of HIF‐1αand HIF‐2αincreased .Tropomyosin 1 (TPM1) met the sequence criteria for microRNA‐target interaction ,which was later confirmed by luciferase reporter system and mutation test in vitro .HK2 cell transfected with pre‐miT‐29c oligonucleotide could inhibit the tropomyosin up‐regulation induced by TGF‐β1 treatment (3 ng/mL ,24 h) , P<0 .05 or 0 .01 .Conclusions :Renal interstitial fibrosis in rat remnant kidney was significant ,and it was accompanied by the miR‐29c down‐regulation .Moderate activation of HIF level may attenuate the deterioration of renal function by up‐regulating miR‐29c expression .

Objective To explore the role of zinc finger protein 36 (ZFP36) in regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and preosteoblasts. Methods ZFP36 expression was observed in primary mouse BMSCs and mouse preosteoblasts (MC3T3-E1 cells) during induced osteogenic differentiation. Zfp36-deficient cell models were constructed in the two cells using RNA interference technique and the changes in differentiation capacities of the transfected cells into osteoblasts were observed. Transcriptome sequencing was used to investigate the potential mechanisms of ZFP36 for regulating osteoblast differentiation of the two cells. U0126, a ERK/MAPK signal suppressor, was used to verify the regulatory mechanism of Zfp36 in osteogenic differentiation of Zfp36-deficient cells. Results During the 14-day induction of osteogenic differentiation, both mouse BMSCs and MC3T3-E1 cells exhibited increased expression of ZFP36, and its mRNA expression reached the peak level on Day 7 (P<0.0001). The Zfp36-deficient cell models showed reduced intensity of alkaline phosphatase (ALP) staining and alizarin red staining with significantly lowered expressions of the osteogenic marker genes including Alpl, Sp7, Bglap and Ibsp (P<0.01). Transcriptome sequencing verified the reduction of bone mineralization-related gene expressions in Zfp36-deficient cells and indicated the involvement of ERK signaling in the potential regulatory mechanism of Zfp36. Immunoblotting showed that pERK protein expression increased significantly in Zfp36-deficient cells compared with the control cells. In Zfp36-deficient MC3T3-E1 cells, inhibition of activated ERK/MAPK signaling with U0126 resulted in obviously enhanced ALP staining and significantly increased expressions of osteoblast differentiation markers Runx2 and Bglap (P<0.05). Conclusions ZFP36 is involved in the regulation of osteoblast differentiation of mouse BMSCs and preosteoblasts, and ZFP36 deficiency causes inhibition of osteoblast differentiation of the cells by activating the ERK/MAPK signaling pathway.

Objective To explore the role of zinc finger protein 36 (ZFP36) in regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and preosteoblasts. Methods ZFP36 expression was observed in primary mouse BMSCs and mouse preosteoblasts (MC3T3-E1 cells) during induced osteogenic differentiation. Zfp36-deficient cell models were constructed in the two cells using RNA interference technique and the changes in differentiation capacities of the transfected cells into osteoblasts were observed. Transcriptome sequencing was used to investigate the potential mechanisms of ZFP36 for regulating osteoblast differentiation of the two cells. U0126, a ERK/MAPK signal suppressor, was used to verify the regulatory mechanism of Zfp36 in osteogenic differentiation of Zfp36-deficient cells. Results During the 14-day induction of osteogenic differentiation, both mouse BMSCs and MC3T3-E1 cells exhibited increased expression of ZFP36, and its mRNA expression reached the peak level on Day 7 (P<0.0001). The Zfp36-deficient cell models showed reduced intensity of alkaline phosphatase (ALP) staining and alizarin red staining with significantly lowered expressions of the osteogenic marker genes including Alpl, Sp7, Bglap and Ibsp (P<0.01). Transcriptome sequencing verified the reduction of bone mineralization-related gene expressions in Zfp36-deficient cells and indicated the involvement of ERK signaling in the potential regulatory mechanism of Zfp36. Immunoblotting showed that pERK protein expression increased significantly in Zfp36-deficient cells compared with the control cells. In Zfp36-deficient MC3T3-E1 cells, inhibition of activated ERK/MAPK signaling with U0126 resulted in obviously enhanced ALP staining and significantly increased expressions of osteoblast differentiation markers Runx2 and Bglap (P<0.05). Conclusions ZFP36 is involved in the regulation of osteoblast differentiation of mouse BMSCs and preosteoblasts, and ZFP36 deficiency causes inhibition of osteoblast differentiation of the cells by activating the ERK/MAPK signaling pathway.

Objective:To analyze the current status of the global burden of stroke disease from 1990 to 2019,to predict the development trend of stroke disease burden in the 30 years from 2020 to 2049,and to provide a basis for formulating national health policies on stroke diseases.Methods:The Global Burden of Disease Study 2019(GBD 2019)database was searched to extract global stroke disease incidence,prevalence,case fatality,and disability-adjusted life years(DALYs)disease burden indicators from 1990-2019,the trends over time were modeled using linear,Poisson,and exponential regressions,prediction and study of the relationship between stroke and sociodemographic index(SDI)based on per capita gross domestic product(GDP)were conducted.Results:The global burden of stroke disease increased significantly from 1990-2019 and is predicted to continue to rise over the next 30 years(2020-2049).In 2049,the global stroke incidence,prevalence,case fatality,and DALYs will increase by 8.53 million(63％),119.83 million(109％),7.79 million(118％)and 118.92 million person-years(79％),respectively,compared with 2019,with a significant increase in the burden of stroke in the elderly population.In the next 30 years,the age-standardized incidence rates of stroke in men and women will be similar,while the age-standardized rates of prevalence in women will be relatively higher,and age-standardized case fatality rates and DALYs in men will be relatively higher.The disease burden of stroke was negatively correlated with SDI.The burden of stroke disease was significantly higher in regions with a low SDI than in regions with a high SDI.Conclusion:The global burden of stroke will increase in the next 30 years,which may be related to the aging of population and closely related to the development of economy.It is necessary to strengthen the prevention of stroke and formulate targeted strategies targeted strategies according to different SDI regions.

To determine the efficacy and safety of selinexor combined with venetoclax (VEN) and azactitidine (AZA) for patients with relapsed and/or refractory acute myeloid leukemia (R/R AML) . Twelve patients with R/R AML treated with selinexor plus VEN and AZA in the Affiliated Cancer Hospital of Zhengzhou University from May 2022 to May 2023 were included. Their clinical data were retrospectively analyzed. Among the 12 R/R AML patients, 5 (41.7%) achieved complete remission (CR) , 1 (8.3%) achieved CR with incomplete hematological recovery, and 5 (41.7%) achieved partial remission. The median time to reach CR was 28 (16-59) days. The median PFS was 61 (15-300) days. The main adverse event of the regimen was hematological toxicity. No chemotherapy-related deaths were observed. The combination of selinexor plus VEN and AZA is an effective treatment for R/R AML patients.

【Objective】 To develop an assay to determine β-lactam antibiotics using microcolumn gels and to study the β-lactam antibiotics present in the blood of patients and their clinical significances. 【Methods】 446 patients with a history of taking β-lactam antibiotics from January 2019 to June 2019 were randomly selected from Trauma Emergency Center, Department of Arthrosis, Department of Spine and Department of Bone Oncology of our hospital, and 4 mL(per capita) venous blood was collected. Irregular antibody screening, anti-globulin detection and drug antibody determination were performed by microcolumn gel method. The data of gender, age, disease, blood transfusion history and medication were collected. The test results and clinical data were retrospective analyzed. 【Results】 The yielding rate of antibody was 0.45%(2/446) in patients with a history of taking β -lactam antibiotics. 16.38%(73/446) of the samples were positive in direct antiglobulin test, and 64.38%(47/73) of them did not agglutinate with RBCs treated with drugs. The yielding rate of specific antibodies against drug was 4.93%(22/446), and the titer ranged from 2 to 128(8). 1 case of auto-IgM antibody, 1 case of blood group related antibody and 2 cases of non-specific protein adsorption were detected. The yielding rate of drug antibody in patients with blood transfusion history reached to 12.10 %(22/124), so it was also high in patients with bone tumor. 【Conclusion】 Direct antiglobulin assay is helpful for the detection of β-lactam antibodies. The negative results of antibody screening cannot completely exclude the presence of drug antibodies. The yielding rate of drug antibody can be greatly improved by specific drug antibody detection, and it was higher in transfused patients relative to non-transfused one.