1.circ_HIPK3 regulates function and morphology of Aβ induced hippocampal neurons by targeting miR-381-3p/ZNF217 axis
Wei LI ; Liang CHEN ; Changying LYU
Tianjin Medical Journal 2024;52(3):237-244
Objective To analyze the influence of cyclic RNA homologous domain interacting protein kinase 3(circ_HIPK3)on function and morphology of myloid β-protein(Aβ)induced hippocampal neurons by targeting miR-381-3p/zinc finger protein 217(ZNF217)axis.Methods Hippocampal neurons of neonatal rats were prepared and divided into the control group,the Aβ group,the si NC1 group,the si HIPK3 group,the si HIPK3+inhibitor NC group,the si HIPK3+miR-381-3p inhibitor group,the si HIPK3+miR-381-3p inhibitor+si NC2 group and the si HIPK3+miR-381-3p inhibitor+si ZNF217 group.Except the control group,all the other groups were modeled by 40 μmol/L Aβ1~42.qRT-PCR was used to determine the circ of hippocampal neurons circ_HIPK3,miR-381-3p and ZNF217 mRNA levels.Cell morphology was observed by transmission electron microscope,and the survival rate of hippocampal neurons was measured by CCK-8 method.Hochesst 33342 method was used to measure apoptosis of hippocampal neurons.The intracellular Ca2+ fluorescence intensity of hippocampal neurons was detected by flow cytometry.The expression levels of P-Tau,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),Caspase-3 and ZNF217 proteins in hippocampal neurons were measured by Western blot assay.Double luciferase reporter genes were used to analyze the targeting relationship between miR-381-3p and circ_HIPK3,ZNF217.Results In the control group,the structure of hippocampal neurons was normal,the morphology of nucleus was normal,and there were no pathological changes in mitochondria and endoplasmic reticulum.In the Aβ group,hippocampal neurons showed degenerative changes,abnormal nuclear morphology,membrane invagination,a large number of mitochondria swelling and a large number of lipid droplets vacuoles in cytoplasm.Compared with the Aβ group,the hippocampal neuronal structure was partially restored in the si HIPK3 group.Compared with the si HIPK3 group,the hippocampal neuronal structure was severely damaged in the si HIPK3+miR-381-3p inhibitor group.Compared with the si HIPK3+miR-381-3p inhibitor group,the damage of hippocampal neurons in the si HIPK3+miR-381-3p inhibitor+si ZNF217 group was reduced.Compared with the control group,the circ_HIPK3,ZNF217 mRNA and ZNF217 protein levels,apoptosis rate,Ca2+ fluorescence intensity,P-Tau,Bax,Caspase-3 protein expression of hippocampal neurons were increased in the Aβ group,and the miR-381-3p level,survival rate and Bcl-2 protein expression decreased(P<0.05).Compared with the Aβ group,the circ_HIPK3,ZNF217 mRNA and ZNF217 protein levels,apoptosis rate,Ca2+ fluorescence intensity,P-Tau,Bax and Caspase-3 protein expression of hippocampal neurons were decreased in the si HIPK3 group,and miR-381-3p level,survival rate and Bcl-2 protein expression increased(P<0.05).Compared with the si HIPK3 group,the circ_HIPK3,ZNF217 mRNA and ZNF217 protein levels,apoptosis rate,Ca2+ fluorescence intensity,P-Tau,Bax and Caspase-3 protein expression of hippocampal neurons in the si HIPK3+miR-381-3p inhibitor group were increased,and the miR-381-3p level,survival rate and Bcl-2 protein expression decreased(P<0.05).Compared with the si HIPK3+miR-381-3p inhibitor group,the ZNF217 mRNA and ZNF217 protein levels,apoptosis rate,Ca2+ fluorescence intensity,P-Tau,Bax and Caspase-3 protein expression of hippocampal neurons in the si HIPK3+miR-381-3p inhibitor+si ZNF217 group were decreased,and the survival rate and Bcl-2 protein expression increased(P<0.05).miR-381-3p targeted and combined with HIPK3 and ZNF217.Conclusion circ_HIPK3 silencing may ameliorate Aβ-induced damage of hippocampal neuronal structure and function by regulating miR-381-3p/ZNF217 axis.
2.Value of renal biopsy in the diagnosis and treatment of adult patients with acute kidney disease
Mengru LYU ; Buyun WU ; Ao BIAN ; Bo ZHANG ; Lin WU ; Jingfeng ZHU ; Bin SUN ; Changying XING ; Huijuan MAO
Chinese Journal of Nephrology 2024;40(3):193-200
Objective:To analyze the changes of diagnosis and treatment before and after renal biopsy in adult patients with acute kidney disease (AKD), and to explore the value of renal biopsy in the diagnosis and treatment of AKD.Methods:It was a single-center retrospective observational study. The adult patients with AKD who underwent renal biopsy in the Department of Nephrology of the First Affiliated Hospital of Nanjing Medical University from January 1, 2017 to December 31, 2021 were enrolled. Demographic data, general clinical data, laboratory tests, and diagnosis and treatment data before and after renal biopsy were collected to analyze the concordance rate between clinical and pathological diagnoses, changes in treatment after renal biopsy, and bleeding complication.Results:A total of 575 patients diagnosed with AKD by renal biopsy were included in this study, with age of 51 (36, 63) years old and 359 males (62.4%). Among them, there were 293 patients (51.0%) of acute kidney injury, 348 patients (60.5%) of hypertension and 124 patients (21.6%) of diabetes. The peak serum creatinine was 272 (190, 477) μmol/L. The hemoglobin was 106 (86, 126) g/L. The 24-hour urine protein was 2.15 (0.79, 4.82) g. There were 347 patients (60.3%) of acute glomerular diseases, 136 patients (23.7%) of acute interstitial nephritis, 47 patients (8.2%) of thrombotic microangiopathy, and 45 patients (7.8%) of acute tubular necrosis. The most common types of acute glomerular diseases were IgA nephropathy and anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, accounting for 22.3% (128/575) and 12.2% (70/575), respectively. The clinical diagnoses before renal biopsy were consistent with the renal histopathological diagnoses in 454 patients, with an accuracy rate of 79.0%. Following the renal biopsy, the treatment plan involving glucocorticoids or immunosuppressants was adjusted in 394 patients (68.5%). Significant post-biopsy bleeding occurred in 15 patients (2.6%), with 12 patients requiring blood transfusion and 1 patient requiring surgical intervention.Conclusions:Twenty-one clinical diagnoses do not match the pathological diagnoses in adult AKD patients, 68.5% of patients have changes in their treatment plans, and 2.6% of patients have significant hemorrhagic complications after renal biopsy. Clinicians need to carefully consider the benefits and risks and make individualized decisions about renal biopsy.
3.Multidisciplinary team for the diagnosis and treatment of congenital band syndrome
Changying ZHAO ; Hang ZHANG ; Lingxia LI ; Yanhong LYU ; Rui SHU ; Yu WANG ; Honghu JIN ; Rui CONG
Chinese Journal of Applied Clinical Pediatrics 2021;36(20):1576-1578
Objective:To explore the significance of multidisciplinary team for the diagnosis and treatment of congenital band syndrome.Methods:Five children with congenital circular band syndrome admitted in the First Affiliated Hospital of the Chinese People′s Liberation Army Air Force Medical University from January 2017 to January 2020 were retrospectively analyzed.They were diagnosed, treated and followed up by a multidisciplinary team including the department of obstetrics and gynecology, ultrasound, and orthopedics from the fetal stage.Results:One case was found with gradually aggravated ring band that affects the blood circulation of distal limbs during fetal examination, who was promptly performed with partial band release under fetoscopy.All cases had Patterson type Ⅰ ring bands at birth, and distal limbs did not have obvious deformity.They were performed with selective annular band resection, and postoperatively followed up for an average of 10.6 (8-13) months.The annular depression of the skin disappeared, and the appearance and function recovered satisfactory.According to the monitoring of side effects scale (Moses), 4 cases were excellent, 1 case was good, and the excellent and good rate was 100%.Conclusions:The multidisciplinary team for the diagnosis and treatment of congenital band syndrome can maximize the professional advantages of physicians with diffe-rent specialties, make early diagnosis and treatment, minimize the compression of the ring band on the limbs, and avoid serious limb deformities.It is worthy of clinical application.
4.Additional role of 99mTc-MIBI SPECT-CT imaging in preoperative localization of parathyroidectomy-clinical analysis of 359 patients with secondary hyperparathyroidism
Ming ZENG ; Wei LIU ; Ningning WANG ; Changying XING ; Huijuan MAO ; Xiangbao YU ; Xiaoming ZHA ; Bin SUN ; Guang YANG ; Bo ZHANG ; Chun OUYANG ; Xiaolin LYU ; Ling WANG ; Qing MA ; Yanyan PAN
Chinese Journal of Nephrology 2017;33(2):86-91
Objective To evaluate the additional role of 99mTc-MIBI SPECT-CT imaging before parathyroidectomy (PTX) for secondary hyperparathyroidism (SHPT) patients.Methods A total of 359 SHPT patients from the First Affiliated Hospital of Nanjing Medical University were enrolled in the study from April 2011 to January 2016.Patients were divided into two groups according to the difference of 99mTc-MIBI imaging techniques preoperatively.Patients in group A had dual-phase 99mTc-sestamibi parathyroid scintigraphy performed only.Patients in group B had SPECT-CT parathyroid scintigraphy added in the early phase.With the parathyroid glands confirmed by pathology after operation being the referencc,scnsitivity,specificity,consistency and surgical success rates of the patients in two groups were compared.Results 359 patients (166 men and 193 women) were enrolled,among which 339 on hemodialysis and 20 on peritoneal dialysis.The average age of those patients was (45.90± 11.20) years and median dialysis age was 84 (60.0,120.0) months.Total detection sensitivity,specificity,consistency in group A (169 patients) were 65.54%,56.52%,65.24% and in group B (190 patients) were 73.84%,84.62%,74.21% respectively.Total sensitivity and consistency were higher in group B than those in group A (P < 0.01),while no difference in total specificity was observed between two groups (P=0.055).In group A,detection sensitivity of parathyroid glands were 47.56%,77.44%,57.14% and 79.88% in right upper gland (RU),right lower gland (RL),left upper gland (LU) and left lower gland (LL) respectively.Consistency in group A were 48.52%,77.51%,56.21% and 78.70% respectively.In group B,sensitivity were 58.33%,83.78%,69.78% and 82.89% in RU,RL,LU and LL respectively.Consistency in group B were 59.47%,84.21%,70.53% and 82.63% respectively.Sensitivity and consistency of upper glands were lower than lower glands in both groups (P < 0.01).When SPECT-CT was added,sensitivity and consistency of upper glands for both sides were higher in group B than those in group A,while no difference of surgical success rates was found between two groups (87.57% vs 92.63%,P=0.107).Conclusion 99mTc-MIBI SPECT-CT can be combined with anatomic image effectively and increase the sensitivity and consistency of total and upper parathyroid glands.It can also make the accurate location of the lesions,which improves the efficiency of the operation.

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