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ObjectiveTo investigate the effect of Rehmanniae Radix Praeparata on neurological function injury in ischemic stroke rats and explore its mechanism. MethodMale SD rats were randomized into sham operation, model, low- and high -dose (3.5 g·kg-1 and 7 g·kg-1) Rehmannia Radix Praeparata, and nimodipine (0.01 g·kg-1) groups. The rat model of middle cerebral artery occlusion (MCAO) was established with the modified suture occlusion method. Zea-Longa 5-point scoring was employed to evaluate the neurological function of rats. The cerebral infarction volume was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hematoxylin-eosin staining and Nissl staining were employed to observe the morphology and damage of the brain tissue. Meanwhile, the serum levels of lactate dehydrogenase (LDH), oxidative stress-related indicators superoxide dismutase (SOD), glutathione peroxidase 4 (GPX4), and malondialdehyde (MDA), and the iron (Fe) content in the brain tissue were determined. To explore the mechanism of Rehmanniae Radix Preparata in mitigating the neurological damage in ischemic stroke rats, Western blotting was employed to determine the expression levels of proteins in the ischemic brain tissue. The autophagy-associated proteins included autophagy effector (beclin-1), microtubule-associated protein light chain 3 (LC3B), and ubiquitin-binding protein p62 (p62). The ferroptosis-associated proteins included transferrin (TF), transferrin receptor 1 (TFR1), ferritin heavy chain 1 (FTH1), and ferropotin (FPN1). The neurological function injury-associated proteins included brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB). ResultCompared with the sham operation group, the model group showed increased neurological function score, cerebral infarction volume, and appearance of nuclear pyknosis and vacuole of cells in the cerebral cortex. In addition, the model group presented elevated levels of LDH, MDA, and Fe (P<0.01) and lowered levels of SOD and GPX4 (P<0.01). Compared with the model group, Rehmanniae Radix Praeparata decreased the content of LDH, MDA, and Fe (P<0.05, P<0.01) and elevated the levels of SOD and GPX4 (P<0.05, P<0.01). Compared with the sham operation group, the modeling promoted the expression of beclin-1,LC3B Ⅱ/Ⅰ, TF, and TFR1 and inhibited the expression of p62, FTH1, FPN1, BDNF, and TrkB (P<0.01). The expression levels of these proteins were recovered after the treatment with Rehmanniae Radix Praeparata. ConclusionRehmanniae Radix Praeparata may inhibit ferroptosis and improve the neurological function in ischemic stroke rats by down-regulating the autophagy level in the brain tissue.
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OBJECTIVE@#To investigate the efficacy of Bushen Huoxue Fang (BSHXF, a traditional Chinese medicine formula) for improving recurrent spontaneous abortion (RSA) in mice and the role of tyrosine kinase (JAK2) and transcriptional activator (STAT3) signaling pathway in its therapeutic mechanism.@*METHODS@#Female CBA/J mice were caged with male DBA/2 mice to establish RSA mouse models, which were randomly divided into model group, dydrogesterone group and BSHXF group, with the female mice caged with male BALB/c mice as the control group (n=6). From the first day of pregnancy, the mice were subjected to daily intragastric administration of BSHXF, dydrogesterone, or distilled water (in control and model groups) for 12 days. After the treatments, serum levels of antithrombin III (AT-III), activated protein C (APC), tissue plasminogen activator (t-PA), progesterone, human chorionic gonadotropin (HCG), and estradiol (E2) were detected in each group using ELISA. HE staining was used to observe the morphological changes of the endometrium of the mice. Western blotting was performed to determine the expressions of p-JAK2, p-Stat3 and Bcl-2 in the placenta of the mice.@*RESULTS@#Compared with the control mice, the mouse models of RSA showed a significantly increased embryo loss rate with decreased serum levels of AT-III, T-PA, progesterone, APC and HCG, increased placental expressions of p-JAK2, p-STAT3 and Bax, and decreased expression of Bcl-2 (P < 0.05). Treatments with BSHXF and dydrogesterone both increased serum levels of AT-III, t-PA and HCG in the mouse models; Serum APC level was significantly reduced in BSHXF group and serum progesterone level was significantly increased in dydrogesterone group (P < 0.05).@*CONCLUSION@#BSHXF can improve the prethrombotic state and inhibit cell apoptosis by downregulating the JAK2/STAT3 pathway to increase the pregnancy rate in mouse models of RSA.
Subject(s)
Animals , Mice , Abortion, Habitual/prevention & control , Signal Transduction , Down-Regulation , Disease Models, AnimalABSTRACT
PURPOSE: Immune checkpoint inhibitors (ICI) in general have shown poor efficacy in bladder cancer. The purpose of this project was to determine whether photodynamic therapy (PDT) with bladder cancer-specific porphyrin-based PLZ4-nanoparticles (PNP) potentiated ICI. EXPERIMENTAL DESIGN: SV40 T/Ras double-transgenic mice bearing spontaneous bladder cancer and C57BL/6 mice carrying syngeneic bladder cancer models were used to determine the efficacy and conduct molecular correlative studies. RESULTS: PDT with PNP generated reactive oxygen species, and induced protein carbonylation and dendritic cell maturation. In SV40 T/Ras double-transgenic mice carrying spontaneous bladder cancer, the median survival was 33.7 days in the control, compared with 44.8 (P = 0.0123), 52.6 (P = 0.0054), and over 75 (P = 0.0001) days in the anti-programmed cell death-1 antibody (anti-PD-1), PNP PDT, and combination groups, respectively. At Day 75 when all mice in other groups died, only 1 in 7 mice in the combination group died. For the direct anti-tumor activity, compared with the control, the anti-PD-1, PNP PDT, and combination groups induced a 40.25% (P = 0.0003), 80.72% (P < 0.0001), and 93.03% (P < 0.0001) tumor reduction, respectively. For the abscopal anticancer immunity, the anti-PD-1, PNP PDT, and combination groups induced tumor reduction of 45.73% (P = 0.0001), 54.92% (P < 0.0001), and 75.96% (P < 0.0001), respectively. The combination treatment also diminished spontaneous and induced lung metastasis. Potential of immunotherapy by PNP PDT is multifactorial. CONCLUSIONS: In addition to its potential for photodynamic diagnosis and therapy, PNP PDT can synergize immunotherapy in treating locally advanced and metastatic bladder cancer. Clinical trials are warranted to determine the efficacy and toxicity of this combination.
Subject(s)
Photochemotherapy , Urinary Bladder Neoplasms , Mice , Animals , Urinary Bladder Neoplasms/therapy , Cell Line, Tumor , Mice, Inbred C57BL , Immunotherapy , Phototherapy , Immunologic Factors , Mice, TransgenicABSTRACT
Objective:The aim of this study was to evaluate the safety and efficacy of prostatistic urethral lift (PUL) in treating benign prostate hyperplasia(BPH) through systematic review and Meta-analysis.Methods:A systematic literature search on CNKI, Wanfang, VIP, PubMed, Web of Science, Cochrane Library and Chinese Clinical Trial Registry to identify the relevant studies and data before September 2021. Information was extracted from each eligible article. All statistical analyses of this Meta-analyses were performed with Review Manager 5.3 and Stata 15.0 software to conduct a Meta-analysis of the symptom improvement of BPH patients before and 3 months and 12 months after PUL. The main evaluation indicators included: International Prostate Symptom Score (IPSS), maximum urinary flow rate (Q max), post-void residual (PVR), and Quality of Life Scale (QOL), Sexual Health Inventory for Men (SHIM). The complication rate of PUL was systematically evaluated. Results:A total of 12 clinical studies were included, and 850 patients accepted the PUL. The results showed that IPSS decreased significantly at both 3 and 24 months after PUL surgery ( MD = -11.77, 95% CI -12.47—-11.07, P<0.05; MD = -9.71, 95% CI-10.76—-8.66, P<0.05), Q max (ml/s) increased to a certain degree ( MD = 3.87, 95% CI 3.37—4.37, P<0.05; MD = 3.68, 95% CI 2.97—4.40, P<0.05), QOL decreased significantly ( MD=-2.57, 95% CI -2.76—-2.38, P<0.05; MD = -2.14, 95% CI -2.38—-2.91, P<0.05), SHIM score was unaffected ( P>0.05), compared with preoperative baseline data. PUL could be performed under local anesthesia, the main perioperative complications reported in the included studies were dysuria (17%±6%), hematuria (14%±5%) and pelvic pain (8%±6%), all of which were transient. Conclusions:PUL in the treatment of BPH has significant short-term and long-term efficacy with low surgical risk and complication rate, and can preserve normal ejaculation function. It is a safe and effective minimally invasive surgery, which can be used for BPH patients with intolerance to general anesthesia surgery or normal sexual function demand.
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The present study investigated the effect of active components of Descurainia sophia on allergic asthma and explored the underlying mechanism. SD male rats were randomly divided into a normal group(NC), a model group(M), a D. sophia decoction group(DS), a D. sophia fatty oil group(FO), a D. sophia flavonoid glycoside group(FG), a D. sophia oligosaccharide group(Oli), and a positive drug dexamethasone group(Y). The allergic asthma model was induced in rats by intraperitoneal injection of ovalbumin(OVA) and aluminum hydroxide gel adjuvant(sensitization) and atomization of OVA solution(excitation). After modeling, asthma-related indicators, tracheal phenol red excretion, inflammatory cell levels in the peripheral blood, lung permeability index(LPI), and oxygenation index(OI) of rats were detected. The pathological changes of lung tissues were observed by HE staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of inflammatory factors immunoglobulin E(IgE), interleukin-4(IL-4), and interferon-γ(IFN-γ) in the bronchoalveolar lavage fluid(BALF) and the content of endothelin-1(ET-1) and angiotensin-converting enzyme(ACE) in lung tissue homogenate. The serum content of nitric oxide(NO) was detected by colorimetry. Western blot was employed to determine the protein expression of Toll-like receptor 4(TLR4), nuclear factor κB-p65(NF-κB-p65), phosphorylated NF-κB-p65(p-NF-κB-p65), myosin light chain kinase(MLCK), vascular endothelial cadherin(VE cadherin), connexin 43, and claudin 5, and the mechanism of active components of D. sophia on allergic asthma was explored. As revealed by the results, the M group showed extensive infiltration of inflammatory cells around the bronchus of the lung tissues of the allergic asthma rats, thickened bronchial wall, severely deformed alveolar structure, increased number of wheezes, the content of IgE, IL-4, ET-1, and ACE, inflammatory cells, and LPI, and reduced latency of asthma, tracheal phenol red excretion, IFN-γ, NO content, and OI. After the intervention of the active components of D. sophia, the DS, FO, FG, Oli, and Y groups showed improved asthma-related indicators, tracheal phenol red excretion, and lung tissue lesions in allergic asthma rats, and the effects in the FO and Oli groups were superior. The content of inflammatory factors in BALF was recovered in the DS, FO, and Y groups and the FG and Oli groups. The number of inflammatory cells in rats was reduced in the DS and FO groups, and the FG, Oli, and Y groups to varying degrees, and the effect in the FO group was superior. DS, FO, Oli, and Y reduced ET-1, ACE, and LPI and increased NO and OI. FG recovered NO, ET-1, ACE, LPI, and OI to improve lung epithelial damage and permeability. Further investigation of inflammation-related TLR4/NF-κB pathways, MLCK, and related skeleton protein levels showed that TLR4, NF-κB-p65, p-NF-κB-p65, and MLCK levels were increased, and VE cadherin, connexin 43, and claudin 5 were reduced in the M group. DS, FO, FG, Oli, and Y could reduce the protein expression related to the TLR4 pathway to varying degrees, and regulate the protein expression of MLCK, VE cadherin, connexin 43, and claudin 5. It is inferred that the active components of D. sophia improve lung permeability in rats with allergic asthma presumedly by regulating the TLR4/NF-κB signaling pathway to improve airway inflammation, mediating MLCK and connexin, and regulating epithelial damage.
Subject(s)
Animals , Male , Rats , Asthma/drug therapy , Bronchoalveolar Lavage Fluid , Inflammation/metabolism , Lung , PermeabilityABSTRACT
Objective:To investigate the role and mechanism of chemokine receptor type 4 (CXCR4) in renal injury and fibrosis caused by calcium oxalate crystals in mice.Methods:In June 2021, Fifteen male C57/BL6 mice were divided into control group (5 mice), model group (5 mice), and AMD3100 intervention group (5 mice) by random number table method. In model group and AMD3100 intervention group, glyoxylate (100 mg/kg) was injected intraperitoneal for 7 consecutive days for modeling. Meanwhile, the AMD3100 intervention group was also given intraperitoneal injection of AMD3100 (1 mg/kg) for 7 days. The control group was continuously injected with equal volume saline intraperitoneally. After 7 days, peripheral blood was collected from each group to determine the levels of serum urea nitrogen (BUN) and creatinine (Scr) to assess the renal function; HE, Von-Kossa, Picrosirius Red staining was also taken from the left kidney to observe the pathological changes of renal tissue. CXCR4, transforming growth factor β1 (TGF-β1) were detected by immunohistochemistry and western blot. The expression levels of PI3K/AKT pathway-related proteins were detected by western blot.Results:The results of biochemical indexes showed that the serum Scr [(108.03±13.56) μmol/L vs. (39.50±4.48)μmol/L, P<0.01)] and BUN[(5.66±0.48)mmol/L vs. (0.77±0.10)mmol/L, P<0.01) levels were significantly increased in model group compared with the control group. The AMD3100 intervention group was significantly lower than the model group in terms of Scr [(65.77±3.27)μmol/L vs. (108.03±13.56)μmol/L, P<0.05) and BUN [(2.97±0.44)mmol/L vs. (5.66±0.48)mmol/L, P<0.05) levels. The results of kidney pathology in mice showed that renal tubules were significantly dilated with inflammatory cell infiltration in the model group compared with the control group, and a large number of calcium oxalate crystals and collagen fibers were deposited. The extent of kidney damage, calcium oxalate crystals and collagen fibers deposition were significantly reduced in the AMD3100 intervention group compared with the model group. The results of western blotting showed that the relative expression of CXCR4(0.639±0.019 vs. 0.158±0.012, P<0.01) and TGF-β1(0.698+ 0.018 vs. 0.314+ 0.015, P<0.05) was significantly increased in the model group compared with the control group. The relative expression of CXCR4(0.322±0.231) in the AMD3100 intervention group compared with the model group (0.322±0.231 vs. 0.639±0.019, P<0.05) and TGF-β1(0.445+ 0.017 vs. 0.698+ 0.018, P<0.05) were significantly decreased. The results of immunohistochemical staining showed the trend of CXCR4 and TGF-β1 expression in each group consistent with the results of protein blotting assay. Western blotting results showed that the expression of p-PI3K (0.613±0.016 vs. 0.213±0.011, P<0.01) and p-AKT(0.149±0.013 vs. 0.047±0.014, P<0.01) was significantly increased in the model group compared with the control group. The expression of p-PI3K in the AMD3100 intervention group compared with the model group (0.292±0.020 vs. 0.613±0.016, P<0.05) and p-AKT (0.098±0.021 vs. 0.149±0.013, P<0.05)was significantly decreased. Conclusion:CXCR4 inhibits calcium oxalate crystal-induced kidney injury and interstitial fibrosis in mice by targeting the PI3K/AKT pathway.
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Diabetes mellitus is a group of complex metabolic disorders which has affected hundreds of millions of patients world-widely. The underlying pathogenesis of various types of diabetes is still unclear, which hinders the way of developing more efficient therapies. Although many genes have been found associated with diabetes mellitus, more novel genes are still needed to be discovered towards a complete picture of the underlying mechanism. With the development of complex molecular networks, network-based disease-gene prediction methods have been widely proposed. However, most existing methods are based on the hypothesis of guilt-by-association and often handcraft node features based on local topological structures. Advances in graph embedding techniques have enabled automatically global feature extraction from molecular networks. Inspired by the successful applications of cutting-edge graph embedding methods on complex diseases, we proposed a computational framework to investigate novel genes associated with diabetes mellitus. There are three main steps in the framework: network feature extraction based on graph embedding methods; feature denoising and regeneration using stacked autoencoder; and disease-gene prediction based on machine learning classifiers. We compared the performance by using different graph embedding methods and machine learning classifiers and designed the best workflow for predicting genes associated with diabetes mellitus. Functional enrichment analysis based on Human Phenotype Ontology (HPO), KEGG, and GO biological process and publication search further evaluated the predicted novel genes.
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To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0-10.0 ng ml
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Objective To evaluate efficacy and safety of retrograde intrarenal stone surgery for treatment of upper urinary calculi.Methods The clinical data of 640 patients with upper urinary tract calculi treated by retrograde intrarenal stone surgery (RIRS) in Renmin Hospital of Wuhan University from April 2016 to January 2019 were retrospectively analyzed.There were 424 males and 216 females.The awerage age was (46.2 ± 12.8) years old,ranging 18 to 76 years old.The maximum diameter of the stone is (1.4 ±0.7) cm,ranging 0.6-3.2 cm.There were 126 cases with inferior calculi and 514 cases with non-lurgical calculi.There were 196 cases with unilateral ureteral calculi,118 unilateral ureteral calculi cases with renal calculi,236 cases with unilateral renal stones,and 90 cases with double kidney stones.104 cases were placed with double J tube before operation and 496 cases were not placed before operation.There were 8 cases of horseshoe kidney,30 cases of isolated kidney with renal insufficiency,4 cases of pelvic ectopic kidney with dysplasia,6 cases of congenital ureteral malformation and 2 cases of sponge kidney.Preoperative average hemoglobin was (133.2 + 5.6) g/L,ranging 126-188 g/L.And average serum creatinine was (84.4 + 12.2) μmol/L,ranging 74-242μmol/L before operation.All patients were treated with general anesthesia under the lithotomy position.The ureteroscopy combined with holmium laser lithotripsy was performed.The 200tμm fiber was used,which the parameters were set as 12-45 W(0.5-1.5 J/10-30 Hz).The stone baskets were used to take stones according to actual conditions.The operation was performed by doctors of the same qualifications.Results All patients underwent successful operation.The mean operation time was (45.6 + 14.6) min.The average postoperative hospitalization was (4.8 ± 1.5) d.The postoperative serious complication rate was 0.9%,including(2 cases of sepsis and 1 case of subcapsular hematoma.Of the 640 patients,596 were admitted to the hospital for a double J tube and 44 were lost of follow-up.552 patients met the stone removal criteria,44 patients did not meet the stone removal criteria for other treatments,such as extracorporeal shock wave lithotripsy,ureteroscopy or observed regularly.The stone-free rate (SFR) was 92.6% (552/596) after 1-3 months.On the first postoperative day,serum creatinine was (76.0 ±10.6) (58-156) μmol/L,and postoperative hemoglobin was (126.4 ±9.6) (120-176) g/L.There was no significant difference in preoperative and postoperative hemoglobin (t =2.02,P =0.064).Preoperative and postoperative creatinine (t =64.76,P < 0.05) was statistically significant.Meanwhile,the stone size (x2 =29.569,P < 0.05) and position (x2 =44.949,P < 0.05) versus SFR the impact was statistically significant.Multivariate regression analysis showed that stone size was not an independent risk factor for stone clearance (P =0.639).The stone position was an independent risk factor for stone clearance (P =0.013).Conclusions RIRS is a reliable treatment for small and medium calculi patients of the upper urinary tract.The curative effect of stone removal is clear,the complications are few,the safety is high.However,there are certain limitations to the efficacy in the treatment of large stones and lower calculi.Lower calculi is the independent risk factor for the treatment of efficacy.
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Objective:To compare the injury of renal blood vessels using different puncture pathways and access sizes.Methods:Between April 2018 and June 2019, eighty fresh pig kidneys were selected to perform percutaneous puncture and dilation, which was used to compare the injury of renal blood vessels with different puncture pathways and access sizes. The puncture pathway included the centerline of the normal renal pyramid (A), centreline of one side pyramid of the fused renal pyramid (FRP) (B), midline of the entire FRP (C) and midline of the renal column (D). The access size included F8, F12, F16, F20, F24 and F30. Histopathological methods were used to analyze the injury of renal blood vessels.Results:The puncture through paths A and B mainly caused injury to the grade Ⅴ and Ⅵ arteries in renal cortex. The puncture often directly injures the grade Ⅳ artery in path C. The puncture often simultaneously injures the grade Ⅲ-Ⅵ arteries in path D. Grade Ⅲ artery injury began to occur when paths A, B, C, and D were dilated to F30, F24, F16, and F12, respectively. The degree of arterial injury among the four different puncture pathways was significantly different in F8, F12, F16, F20, F24 and F30 ( P<0.05). Statistical differences were found between paths A and D in F12, F16, F20, F24 and F30 ( P<0.05), and between paths A and C in F16, F20 and F24 ( P<0.05). No significant difference was found between paths A and B in all access sizes ( P>0.05). Compared with F8, the degree of arterial injury of the F30 in path A and the F24 and F30 in path B were increased significantly ( P<0.05). Conclusions:Vascular injury in path D was the most serious followed by that in path C. Relatively little vascular injury can be achieved in paths A and B. The vascular injury increased when the path B was dilated to F24, while the path A needed to be dilated to F30.
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Objective@#To evaluate efficacy and safety of retrograde intrarenal stone surgery for treatment of upper urinary calculi.@*Methods@#The clinical data of 640 patients with upper urinary tract calculi treated by retrograde intrarenal stone surgery (RIRS) in Renmin Hospital of Wuhan University from April 2016 to January 2019 were retrospectively analyzed. There were 424 males and 216 females. The awerage age was (46.2±12.8) years old, ranging 18 to 76 years old. The maximum diameter of the stone is (1.4±0.7) cm, ranging 0.6-3.2 cm. There were 126 cases with inferior calculi and 514 cases with non-lurgical calculi. There were 196 cases with unilateral ureteral calculi, 118 unilateral ureteral calculi cases with renal calculi, 236 cases with unilateral renal stones, and 90 cases with double kidney stones. 104 cases were placed with double J tube before operation and 496 cases were not placed before operation. There were 8 cases of horseshoe kidney, 30 cases of isolated kidney with renal insufficiency, 4 cases of pelvic ectopic kidney with dysplasia, 6 cases of congenital ureteral malformation and 2 cases of sponge kidney. Preoperative average hemoglobin was (133.2±5.6)g/L, ranging 126-188 g/L.And average serum creatinine was (84.4±12.2)μmol/L, ranging 74-242μmol/L before operation. All patients were treated with general anesthesia under the lithotomy position. The ureteroscopy combined with holmium laser lithotripsy was performed.The 200μm fiber was used, which the parameters were set as 12-45 W(0.5-1.5 J/10-30 Hz). The stone baskets were used to take stones according to actual conditions. The operation was performed by doctors of the same qualifications.@*Results@#All patients underwent successful operation. The mean operation time was (45.6±14.6)min. The average postoperative hospitalization was (4.8±1.5)d. The postoperative serious complication rate was 0.9%, including(2 cases of sepsis and 1 case of subcapsular hematoma. Of the 640 patients, 596 were admitted to the hospital for a double J tube and 44 were lost of follow-up. 552 patients met the stone removal criteria, 44 patients did not meet the stone removal criteria for other treatments, such as extracorporeal shock wave lithotripsy, ureteroscopy or observed regularly. The stone-free rate (SFR) was 92.6% (552/596) after 1-3 months. On the first postoperative day, serum creatinine was (76.0±10.6)(58-156) μmol/L, and postoperative hemoglobin was (126.4±9. 6)(120-176) g/L. There was no significant difference in preoperative and postoperative hemoglobin (t=2.02, P=0.064). Preoperative and postoperative creatinine (t=64.76, P<0.05) was statistically significant. Meanwhile, the stone size (χ2=29.569, P<0.05) and position (χ2=44.949, P<0.05) versus SFR the impact was statistically significant. Multivariate regression analysis showed that stone size was not an independent risk factor for stone clearance (P=0.639). The stone position was an independent risk factor for stone clearance (P=0.013).@*Conclusions@#RIRS is a reliable treatment for small and medium calculi patients of the upper urinary tract. The curative effect of stone removal is clear, the complications are few, the safety is high. However, there are certain limitations to the efficacy in the treatment of large stones and lower calculi. Lower calculi is the independent risk factor for the treatment of efficacy.
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Patient-derived xenografts (PDXs) are widely recognised as a more physiologically relevant preclinical model than standard cell lines, but are expensive and low throughput, have low engraftment rate and take a long time to develop. Our newly developed conditional reprogramming (CR) technology addresses many PDX drawbacks, but lacks many in vivo factors. Here we determined whether PDXs and CRCs of the same cancer origin maintain the biological fidelity and complement each for translational research and drug development. Four CRC lines were generated from bladder cancer PDXs. Short tandem repeat (STR) analyses revealed that CRCs and their corresponding parental PDXs shared the same STRs, suggesting common cancer origins. CRCs and their corresponding parental PDXs contained the same genetic alterations. Importantly, CRCs retained the same drug sensitivity with the corresponding downstream signalling activity as their corresponding parental PDXs. This suggests that CRCs and PDXs can complement each other, and that CRCs can be used for in vitro fast, high throughput and low cost screening while PDXs can be used for in vivo validation and study of the in vivo factors during translational research and drug development.
Subject(s)
Urinary Bladder Neoplasms/drug therapy , Xenograft Model Antitumor Assays/methods , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Culture Techniques/economics , Cell Culture Techniques/methods , Disease Models, Animal , Drug Development , Drug Resistance, Neoplasm , Humans , Mice , Mutation , Translational Research, Biomedical , Tumor Cells, Cultured , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Xenograft Model Antitumor Assays/economicsABSTRACT
This study aimed to compare the clinical outcomes between transurethral thulium laser enucleation of the prostate (ThuLEP) and transurethral thulium laser resection of the prostate (ThuLRP) for treating benign prostatic hyperplasia (BPH). From May 2014 to August 2015, 212 patients underwent ThuLRP and 188 patients underwent ThuLEP. The ThuLEP group was further divided into two subgroups according to the ways the prostate was taken out. The perioperative parameters were recorded and analyzed. The international prostate symptom score (IPSS), quality-of-life (QoL) score, maximum flow rate (Qmax), and postvoid residual urine volume (PVR) in both groups were estimated and compared 3, 6, and 12 months after surgery. No significant difference was observed between the groups in terms of irrigated time, irrigated volume, catheterization time, and hospital stay. However, the significantly lower hemoglobin drop was observed in the ThuLRP group compared with the ThuLEP group. The ThuLEP group with a morcellator required a shorter operation time for patients with large prostate volume (> 60 mL) compared with the ThuLRP and ThuLEP groups without a morcellator. During 12 months of follow-up, IPSS, Qmax, QoL, and PVR improved significantly without significant differences between the groups. No severe complications were reported; however, the occurrence of transient urge incontinence was higher after ThuLEP compared with ThuLRP, and the proportion of urinary tract infection after surgery was higher in ThuLRP than in ThuLEP. ThuLRP and ThuLEP are safe and efficient for treating patients with symptomatic BPH. ThuLRP offers advantages in terms of minimal blood loss.
Subject(s)
Laser Therapy , Prostatic Hyperplasia/surgery , Thulium/therapeutic use , Transurethral Resection of Prostate , Humans , Laser Therapy/adverse effects , Length of Stay , Light , Male , Middle Aged , Operative Time , Organ Size , Postoperative Complications/etiology , Prostatic Hyperplasia/pathology , Retrospective Studies , Treatment OutcomeABSTRACT
This study compared the diagnostic efficacy of transrectal ultrasound (TRUS)-guided prostate biopsy (TRBx) and transperineal prostate biopsy (TPBx) in patients with suspected prostate cancer (PCa). We enrolled 2962 men who underwent transrectal (n = 1216) or transperineal (n = 1746) systematic 12-core prostate biopsy. Clinical data including age, prostate-specific antigen (PSA) level, and prostate volume (PV) were recorded. To minimize confounding, we performed propensity score-matching analysis. We measured and compared PCa detection rates between TRBx and TPBx, which were stratified by clinical characteristics and Gleason scores. The effects of clinical characteristics on PCa detection rate were assessed by logistic regression. For all patients, TPBx detected a higher proportion of clinically significant PCa (P < 0.001). Logistic regression analyses illustrated that PV had a smaller impact on PCa detection rate of TPBx compared with TRBx. Propensity score-matching analysis showed that the detection rates in TRBx were higher than those in TPBx for patients aged >- 80 years (80.4% vs 56.5%, P = 0.004) and with PSA level 20.1-100.0 ng ml-1 (80.8% vs 69.1%, P = 0.040). In conclusion, TPBx was associated with a higher detection rate of clinically significant PCa than TRBx was; however, because of the high detection rate at certain ages and PSA levels, biopsy approaches should be optimized according to patents' clinical characteristics.
Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Age Factors , Biopsy/methods , Logistic Models , Neoplasm Grading , Perineum , Propensity Score , Prostate/pathology , Prostate-Specific Antigen/blood , Prostatic Neoplasms/pathology , RectumABSTRACT
Objective To analyze the anatomical structure and distribution of the fused renal pyramid (FRP) in cadaveric kidney,and discuss its appearances by CT and ultrasonic examinations.Methods From June 2018 to September 2018,108 cadaveric kidneys were proceeded for regional anatomy.The distribution and anatomical manifestations of FRP was recorded.The renal pyramid was sliced and HE stained to explore the vascular distribution in FRP.From October 2018 to January 2019,ultrasound imaging data of 112 patients with 224 kidneys were collected,including 60 males and 52 females,age (39.0 ± 15.1),ranging from 16 to 73 years old.The renal imaging data of 89 patients and 178 patients with enhanced renal CT were collected,including 48 males and 41 females.Age (45.4 ± 13.6),ranging from 23 to 69 years old.The imaging findings of FRP in ultrasound and enhanced CT was summarized.Results In cadaver kidneys,the proportion of FRP in upper and lower calyces was 68.6% (74/108) and 64.8% (70/108),respectively,higher than that in middle calyces 34.3% (37/108).In the middle group,the incidence of mild fusion was 39.0% (16/41) and severe fusion was 48.8% (20/41).The incidence of fusion of two renal pyramidal structures was 90.2% (37/41).HE staining showed that the boundary between the artery in FRP and the surrounding renal pyramidal was unclear,and the protection of connective tissue was lacking.In Ultrasound,the FRP presented as a large trapezoidal hypo-echoic area with red and blue color signals in doppler mode.In ultrasound,the incidence of FRP was 18.8% (42/224).In enhanced CT,the FRP presented as enhanced cord-like high density shade in large low density area in cortex phase.In enhanced CT,the incidence of FRP 27.5% (49/178).Conclusions The FRP is a common structure in human kidney.The arteries localize within the FRP and are absence of sufficient connective tissue protection which are different from normal arteries.Ultrasound and enhanced CT have recognition ability for FRP.
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Objective To investigate the CT and MRI finding of extrapleural solitary fibrous tumor (ESFT) to improve the preoperative diagnostic ability of such tumors. Methods The clinical data and CT/MRI finding of 11 ESFT patients confirmed by pathology from January 2007 to June 2018 in Jiaxing Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medicine University were retrospectively analyzed. CT scan was performed in 9 cases and MRI scan in 4 cases. Results Of the 11 patients with ESFT, 6 cases occurred in the abdominal cavity, 3 cases in the cavitas pelvis and 2 cases in the ocular region. All the tumors were solitary, and the maximum diameter of the lesion was (8.3 ± 4.2) cm. The boundary of the tumor was clear in 7 cases, and the boundary was not clear in 4 cases. The tumor form was circular or fusiform in 6 cases and lobulated in 5 cases (some tumors had notch sign). CT scanning presented isodensity or inhomogeneous low density, including 4 cases of cystic degeneration accompanied by inner grid separation, and 3 cases of patchy calcification. The enhanced scanning mass showed 6 cases of geographic enhancement and 7 cases of earthworm drilling soil. MRI T1WI showed slightly lower signal intensity; T2WI fat-suppression sequences showed slightly higher mixed signal intensity in 2 cases and an iso-to high mixed signal intensity in 2 cases; and DWI showed uneven high signal intensity in 3 cases. The solid part of the enhanced scanning showed'fast enhancement and slow washout'. Conclusions ESFT is usually manifested as isolated mass, and its CT and MRI finding has certain characteristics, especially in the diagnosis and differential diagnosis of the disease, such as geographic enhancement and earthworm drilling soil signs.
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Objective To evaluate the safety and efficacy of flexible ureteroscopy lithotripsy (FURL) for the treatment of renal stone in solitary kidney patients.Methods The clinical data of 46 patients of solitary kidney,who were treated with FURL from March 2015 to May 2018 in our hospital,were analyzed retrospectively.There were 34 males and 12 females,aged (48.6 ± 9.6) years.Maximum diameter of stone was (15.3 ±4.8) mm,and 29 cases in left kidney and 17 cases in right.34 cases were non-renal calcaneal calculi,12 cases were subrenal calyceal stones.There were 3 cases of congenital solitary kidney,31 cases of functional solitary kidney (contralateral kidney GFR < 10 ml/min) and 12 cases of acquired solitary kidney (7 cases of renal calculi,4 cases of tumor,1 case of tuberculosis).The mean reoperative serum creatinine was (116.38 ± 25.77)μmol/L.All patients were treated with general anesthesia,lithotomy,soft ureteroscopy combined with holmium laser lithotripsy,and assisted lithotripsy.All operations were performed by the same surgeon.The data of operation time,hospital stay,blood loss,renal function before and after operation,postoperative complications and stone clearance rate were recorded.Results In this study,46 cases of the operation were successfully completed.The mean operation time was (58.6 ±16.4) min,the average hospitalization time was (5.6 ± 1.4) days.The mean hemoglobin was decreased (1.4 ± 0.9) g/L.The mean operative time was (58.6 ± 16.4) min.The average postoperative hospitalization time was (5.6 ± 1.4) days.The Postoperative hematuria occurred in 32 cases,low back pain in 3 cases and fever in I case.Stone-free reached in 39 of 46 patients,the stone-free rate(SFR)of primary operation was 84.8% (39/46).There were 7 cases of residual calculi,five patients were treated with secondary FURL,2 patients were required conservative treatment.The SFR was 95.7% (44/46) after the second stage operation.The mean serum creatinine was (112.29 ± 20.62) μ mol/L on the first day after operation,which was not different statistically with that before operation (P =0.177).The mean serum creatinine was (81.54 ± 10.75) μmol/L one month after operation,which was significantly lower than preoperative and 1 day postoperative (P < 0.05).Conclusions FURL could be a safe and effective treatment for renal stone in solitary kidney patients.It has a definite stone-free effect,low incidence of complications.
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Objective@#To analyze the anatomical structure and distribution of the fused renal pyramid (FRP) in cadaveric kidney, and discuss its appearances by CT and ultrasonic examinations.@*Methods@#From June 2018 to September 2018, 108 cadaveric kidneys were proceeded for regional anatomy. The distribution and anatomical manifestations of FRP was recorded. The renal pyramid was sliced and HE stained to explore the vascular distribution in FRP. From October 2018 to January 2019, ultrasound imaging data of 112 patients with 224 kidneys were collected, including 60 males and 52 females, age (39.0±15.1), ranging from 16 to 73 years old. The renal imaging data of 89 patients and 178 patients with enhanced renal CT were collected, including 48 males and 41 females. Age (45.4±13.6), ranging from 23 to 69 years old. The imaging findings of FRP in ultrasound and enhanced CT was summarized.@*Results@#In cadaver kidneys, the proportion of FRP in upper and lower calyces was 68.6% (74/108) and 64.8% (70/108), respectively, higher than that in middle calyces 34.3% (37/108). In the middle group, the incidence of mild fusion was 39.0% (16/41) and severe fusion was 48.8% (20/41). The incidence of fusion of two renal pyramidal structures was 90.2% (37/41). HE staining showed that the boundary between the artery in FRP and the surrounding renal pyramidal was unclear, and the protection of connective tissue was lacking. In Ultrasound, the FRP presented as a large trapezoidal hypo-echoic area with red and blue color signals in doppler mode. In ultrasound, the incidence of FRP was 18.8% (42/224). In enhanced CT, the FRP presented as enhanced cord-like high density shade in large low density area in cortex phase. In enhanced CT, the incidence of FRP 27.5%(49/178).@*Conclusions@#The FRP is a common structure in human kidney. The arteries localize within the FRP and are absence of sufficient connective tissue protection which are different from normal arteries. Ultrasound and enhanced CT have recognition ability for FRP.
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Objective To evaluate the safety and efficacy of ultrasound-guided transperitoneal PCNL for treatment of renal calculi in pelvic ectopic kidney.Methods The clinical data of 4 cases of pelvic ectopic kidney treated in our hospital from June 2016 to August 2017 were retrospectively analyzed.The patient's age ranged from 30 to 67 years with an average of 47.25 years.There were two male and two female patients.2 cases suffered with left pelvic ectopic kidney stones.One case had right pelvic horseshoe ectopic kidney stones and one case had spinal deformity left pelvic ectopic kidney stones.Multiple stones were found in 2 cases.The mainly stones located in the renal pelvis in one case.Multiple stones in the lower calyx was found in another case.The remaining 2 cases had single stones in the renal pelvis.Stone size was 3.4 cm × 2.1 cm,3.0cm×2.1 cm,2.8 cm×2.4 cm and 2.1 cm×1.9 cm respectively.And 1 case with renal calculi in left pelvic ectopic kidney had a history of open surgerv 11 years ago because of the same situation with pelvic ectopic kidney calculi.In this study,all operation was performed under general anesthesia.The ultrasound-guided percutaneous nephrolithotomy combined with preoperative CTU and intraoperative color Doppler ultrasound was used to find the target renal calyx or renal pelvis.And a certain pressure was applied to the abdominal wall to make the intestinal canal deviate from the surface of the pelvic ectopic kidney as much as possible.Under ultrasound real-time detection,it was punctured into the target renal calyx or renal pelvis to find and break stones.And F6 double J tube and F18 nephrostomy tube were left.Operative and post-operative related details (stone free,bleeding,abdominal infection) were reviewed.Results Stone free rate were 100% (4/4).The time of operation and hospital stay were 62,59,55,51 min and 6,6,5,5 days,respectively.None had significant intraoperative and postoperative complications,including haemorrhage,injury of mesenteric vessels,abdominal infection and hydrops.No one left residual stones during 1 month and 3 nonths of follow-up.Conclusions The ultrasound-guided transperitoneal PCNL is a safe and effective procedure for the treatment of patients with renal calculi in pelvic ectopic kidney.
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Objective To explore the clinical significance of fused renal pyramid (FRP) structure in the establishment of percutaneous renal access.Methods From May 2017 to April 2018,10 fresh porcine kidneys were selected to cast in blood vessels for grading the kidney artery.Then another 80 isolated porcine kidueys were used to simulate percutaneous renal pu ncture and dilatation to establish F24 operative access by the same surgeon.Under the endoscope and microscope,we compared the effects of four different puncture paths on the occurrence of renal vascular injury when respectively punctured through the normal renal pyramid (group A),the side of the FRP (group B),the centre of the FRP (group C) and the renal column (group D).Results The kidney arteries can be divided into six grades,there is grade Ⅳ branchinterlobar artery walking inside the FRP.The diameter of interlobar artery in the FRP was significantly smaller than that in the renal column (0.442 ±0.012) mm vs.(0.778 ±0.037) mm,(P <0.001).Endoscopic observation and pathological tissue section showed the following results.In group A,there was no injured blood vessel distributed along the access.There were six specimens with grade Ⅴ or Ⅵ arteries injury in the cortex.Owing to the small size of the renal pyramid and the inaccurate location of the puncture,there was also injury associated with a normal grade Ⅳ artery in the renal column.In group B,there was a certain distance between the tract and the grade Ⅳ artery that distributed in the FRP,injury was still noticed in four specimens.And six specimens have grade Ⅴ/Ⅵ arterial injury.As the distance between the tract and the renal column decreased,there was a case in which a simultaneously injury occurred to the extremity of a grade Ⅲ artery and a grade Ⅳ artery.In group C,there was a white thin strip of connective tissue exposed along the puncture tract.Ectopic grade Ⅳ artery injury occurred in fourteen specimens,and grade Ⅴ/Ⅵ artery injury occurred in seven specimens.In group D,there were grade Ⅲ to Ⅵ arteries distributed along the operational access,which was cowered with white fat and connective tissue.The number of arteryinjury in grades Ⅲ,Ⅳ,and Ⅴ/Ⅵ were4,19,and 5,respectively.The mean ranks of artery injury degree in groups A (17.0),B (30.1),C (33.5) and D (41.5) gradually increased,and the difference was significant (P =0.006).There was a significant difference between group A and C (P =0.018),while no significant difference between group A and B (P =0.122),groups C and D (P =0.072).The proportion of grade Ⅳ artery injury in group A,B,and C was 5% (1/20),25% (5/20),and 70% (14/20),respectively.There was a significant difference between group A and C (P =0.029),while no significant difference between group A and B (P =0.316).There was no significant difference in the injury of grade Ⅴ and Ⅵ artery in four groups (P =0.827).Conclusions When establishing a percutaneous renal access,vascular injury caused bv puncturing through the FRP cannot be ignored.It is necessary to carefu lly identify and bypass the FRP when selecting the puncture path.If unavoidable,the puncture path shoull be on the centreline of one side pyramid of the FRP.