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Objective:To evaluate the feasibility, safety, treatment outcome, and the individualized surgical procedure selection of the interventional treatments of chylous leakage.Methods:From July 2019 to January 2022, the clinical data of 60 consecutive patients with chylous leakage underwent interventional treatment were respectively analyzed. The cases included chylothorax ( n=37), chylous ascites ( n=10), chyluria ( n=4), chylothorax combined with chylous ascites ( n=5), chylothorax combined with chylopericardium ( n=2), and pelvic chylous effusion ( n=2). Conservative treatment was considered to have failed for all patients. The lymphangiography was firstly performed to detect chylous leakage, then an individualized procedure was selected according to the lymphangiography results. The treatment outcomes and complications were recorded, and follow-up was performed. Results:Lymphangiography was technically successful in 55 of 60 patients (91.7%), and no cisterna chyli and thoracic duct opacification was observed in 5 patients. The procedures for the patients included lymphangiography alone ( n=23), thoracic duct embolization ( n=23), thoracic duct disruption ( n=5), lymphatic embolization for pelvic chylous effusion ( n=4), and balloon plasty for thoracic duct ( n=5). Clinical success was achieved in 53 of 60 cases (88.3%). The complication rate was 8.3% (5/60), and all complications were minor. The median follow-up time was 11 months (range 0.5-30 months) for 56 patients, and 4 patients were lost to follow-up. There was one patient presenting the reoccurrence of symptom, and 8 patients died. Conclusions:The interventional treatment of chylous leakage is safe with good outcomes and low complication rate. Individualized treatment procedures based on the lymphangiography findings is feasible and with good curative effect.
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Objective:To evaluate the diagnostic performance and clinical significance of SLE-DAS in the disease activity of SLE patients in China.Methods:The clinical data of 134 patients with SLE were collected. The disease activity was evaluated by SLE-DAS, SLEDAI-2000, BILAG-2004 and PGA scoring tools. Pearson test and Spearman test were used to analyze the correlation. The receiver operating characteristic curve (ROC curve) was used to evaluate SLE-DAS, and Kappa consistency test was adapted to assess the consistency of the two scoring methods.Results:One hundred and thirty-four patients with SLE, including 7 males and 127 females, aged 13-77 years, with an average of (35±13) years were included. Among them, renal involvement was 38.1%, skin mucosal involvement was 11.2%, musculoskeletal involvement was 8.2%, blood system involvement was 13.4%, heart and lung involvement was 2.2%, neuropsychiatric involvement was 1.5%, and multisystem involvement was 3.0%. SLE-DAS was positively correlated with CRP, ESR, anti-dsDNA antibody, urinary protein (24 h) level, SLEDAI-2000, BILAG-2004 and PGA ( r=0.25, 0.34, 0.47, 0.77, 0.93, 0.94, 0.95, P<0.01); SLE-DAS was negatively correlated with PLT, Hb, C3 and C4 ( r=-0.29, -0.43, -0.41, -0.32, P<0.01). When SLEDAI-2000>5 was used as a cut point for analyzing SLE-DAS, the results showed that the area under the curve (AUC) 95% CI of SLE-DAS was 0.961 (0.927,0.995), the Yoden index was 0.845. When the cut-off value was set up to 4.65( P<0.001), the sensitivity was 98.11%, the specificity was 86.42%, and the accuracy was 91.04%. Kappa consistency test showed that kappa value was 0.819( P<0.001). Conclusions:SLE-DAS can be used to evaluate the disease activity of SLE patients and can be used as the evidence to guide treatment plan in clinical practice.
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Objective:To evaluate the correlation between anti-C1q antibody and disease activity and cellular immune function in patients with systemic lupus erythematosus (SLE).Methods:The clinical data and test indexes of 134 patients with SLE and 90 healthy people who were admitted to Henan Provincial People′s Hospital from June 2017 to February 2018 were collected. The level of anti-C1q antibody was measured by enzyme-linked immunosorbent assay (ELISA), and lymphocyte subsets were measured by flow cytometry. According to the score of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, SLE patients were divided into active and inactive groups, and SLE patients were divided into LN group and non-LN group according to the presence or absence of kidney involvement. The levels of anti-C1q antibodies and lymphocyte subsets were compared among the three groups, and correlations between anti-C1q antibodies and disease activity and lymphocytes were analyzed. The predictive value of anti-C1q antibodies and anti double stranded DNA (dsDNA) antibodies for SLE disease activity was evaluated.Results:The anti-C1q antibody level, percentage of T cells and Ts cells in SLE group were higher than those in control group, while the percentage of Th cells, percentage of NK cells, T cell count, Th cell count, B cell count and NK cell count in SLE group were lower than those in control group (all P<0.05); The anti-C1q antibody level in the active group was higher than that in the inactive group, and the counts of T cells, Ts cells, Th cells, B cells and NK cells were lower than those in the inactive group (all P<0.05); The anti-C1q antibody level in LN group was higher than that in non-LN group, and the T cell count, Ts cell count, Th cell count, B cell count, NK cell count were lower than that in non-LN group, with statistically significant difference (all P<0.05). Correlation analysis showed that age, hemoglobin (HB), C3, C4, T cell count, Th cell count, B cell count and NK cell count were negatively correlated with anti-C1q antibody, while SLEDAI-2K, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and anti-dsDNA antibody were positively correlated with anti-C1q antibody (all P<0.05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of anti-C1q antibody alone in predicting SLE disease activity was 0.702, with a sensitivity of 0.547 and a specificity of 0.827. The combination of anti-C1q and anti ds-DNA antibodies resulted in an AUC of 0.761, a sensitivity of 0.756, and a specificity of 0.691. The combined detection value of the two antibodies predicting SLE disease activity was better than the single detection. Conclusions:Anti-C1q antibody is closely related to disease activity and cellular immune dysfunction, and has certain predictive value in SLE disease activity.
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@#Objective To analyze the safety and effectiveness of minimally invasive small incision through the right third intercostal and standard aortic valve replacement. Methods The clinical data of 123 patients with the first simple aortic valve replacement in our hospital from June 2013 to May 2020 were retrospectively analyzed. The patients receiving aortic valve replacement through the right third intercostal small incision were allocated to a minimally invasive group, and patients receiving aortic valve replacement through the median sternal incision were allocated to a common group. The clinical outcomes of the two groups were compared. Results There were 40 patients in the minimally invasive group, including 11 (27.5%) females and 29 (72.5%) males, aged 54.60±9.98 years with the body mass index (BMI) of 23.16±2.48 kg/m2. There were 83 patients in the common group, including 27 (32.5%) females, 56 (67.5%) males, aged 58.77±9.71 years, with the BMI of 24.13±3.13 kg/m2. Compared with the common group, the aortic cross-clamping time, cardiopulmonary bypass time, and operation time were longer (P<0.05), the ventilator support time was shorter (P<0.05), and the blood loss, postoperative 24 h chest drainage volume and total expense were less (P<0.05) in the minimally invasive group. The ICU stay, postoperative hospital stay, and total hospital stay were not statistically different between the two groups (P>0.05). Conclusion The aortic valve replacement through the right third intercostal small incision is safe and effective, with less blood loss, 24 h chest drainage volume and invasiveness.
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Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‒49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‒17.9%, which was significantly higher than that (6.9%‒7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
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Humans , Apoptosis Inducing Factor/metabolism , NAD/metabolism , Dimerization , ApoptosisABSTRACT
Objective To investigate the effect of systematic graded rewarming pattern on all-cause mortality of hypothermic trauma patients in different time periods. Methods A prospective case-control study was carried out for 236 hypothermic trauma patients with modified trauma score<12 in the Emergency Department of the Second Affiliated Hospital of Wenzhou Medical University from January 2020 to December 2021.The patients were randomly assigned into a systematic graded rewarming group (n=118) and a traditional rewarming group (n=118).The main outcome event was all-cause death within 15 days after trauma,and the secondary outcome event was all-cause death within 3,7,and 30 days after trauma. Results Overall,13.98%(33/236) and 14.83%(35/236) of the patients died within 15 and 30 days after trauma,respectively,and the median survival time of all dead patients was 6 (4,10) days.The systematic graded rewarming group had higher temperature after rewarming for 2 h (P=0.001) and larger temperature change after rewarming intervention (P=0.047) than the traditional rewarming group.The all-cause mortality within 15 days (27.3%vs.72.7%,P=0.005) and 30 days (25.7%vs.74.3%,P=0.002) in the systematic graded rewarming group was lower than that in the traditional rewarming group.Kaplan-Meier analysis showed that the survival time of the patients in the systematic graded rewarming group was longer than that in the traditional rewarming group (P=0.003).Multivariate cox regression analysis indicated that systematic graded rewarming was a strong protective factor for survival time after trauma (HR=0.450, P=0.042).Further Logistic regression analysis for the occurrence of all-cause death in each time period showed that the OR of systematic graded rewarming pattern to all-cause death within 15 days and 30 days after trauma were 0.289 and 0.286,respectively,after adjusting the covariates(P=0.008,P=0.005).The temperature after rewarming for 2 h had a negative correlation with all-cause mortality within 30 days after trauma (OR=0.670, P=0.049). Conclusions Systematic graded rewarming is a protective factor for the survival time of patients with traumatic hypothermia and an independent factor affecting the risk of all-cause death within 15 days and 30 days after trauma.The temperature after rewarming for 2 h is expected to be an independent predictor of all-cause mortality of 30 days after trauma in the patients with hypothermia.The systematic graded rewarming pattern could reduce the mortality of hypothermic trauma patients.
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Humans , Hypothermia , Rewarming , Case-Control StudiesABSTRACT
Objective: To explore the expression of miR1290 in endometrial cancer tissues and its relationship with the pathological grade, and to find out the effect of miR1290 on biological characteristics of endometrial cancer cells and its mechanism. Methods: A total of 38 cases of endometrioid adenocarcinoma tissues, 10 cases of adjacent tissues and 23 cases of normal endometrial tissues were collected in Provincial Hospital Affiliated to Shandong University from May 2020 to October 2020. The expression of miR1290 was detected by reverse transcription polymerase chain reaction (RT-PCR). The expressions of miR1290 in endometrial cancer cells including KLE and Ishikawa were knocked down by lentiviral transfection. Cell counting kit 8 (CCK-8) test and colony formation test were used to detect cell proliferation ability, wound healing and Transwell test were used to detect cell invasion and migration ability, western blot was used to detect the expressions of epithelial-mesenchymal transition (EMT), phospholipids acylinositide 3-kinase (PI3K)/Akt and Wnt/β-catenin pathway related proteins. Results: The relative expressions of miR1290 in endometrial cancer tissues were 5.40±3.20, which was 1.55 times of normal endometrial tissues (P<0.01) and 1.75 times of adjacent tissues (P<0.01). The relative expressions of miR1290 in 17 cases of endometrial tissues at proliferative stage and 6 cases of endometrial tissues at secretory stage were 3.00±1.08 and 4.97±0.58, respectively, and the difference was statistically significant (P<0.01). In KLE cells and Ishikawa cells, the expression of miR1290 in miR1290 knockdown (Sh-miR1290) group was decreased when compared with the negative control (Sh-NC) group. The absorbance value of Sh-miR1290 group detected by the CCK-8 method and the colony formation rate detected by the colony formation experiment were both increased, the number of cells penetrating the basement membrane in the Transwell experiment and the wound healing rate in the scratch experiment were decreased (P<0.05). In KLE cells, knockdown of miR1290 reduced the expressions of EMT-related proteins including N-cadherin, Vimentin, Snail and Slug(P<0.05), and the expressions of PI3K and P-Akt/Akt (P<0.05), while there was no significant change in the expressions of Wnt and β-catenin (P>0.05). In Ishikawa cells, knockdown of miR1290 decreased the expressions of EMT-related proteins including N-cadherin, Snail and Slug, and the expressions of Wnt and β-catenin, increased the expression of E-cadherin (P<0.05), while there was no significant change in the expressions of PI3K and P-Akt/Akt (P>0.05). Conclusions: The expressions of miR1290 in endometrial cancer tissues are higher than that in the adjacent tissues and normal endometrial tissues. Knockdown of miR1290 expression can promote the proliferation of endometrial cancer cells, but inhibit cell invasion, migration and EMT ability through the PI3K/Akt and Wnt/β-catenin pathways.
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Female , Humans , Cell Line, Tumor , Cell Movement , Cell Proliferation , Endometrial Neoplasms/genetics , Epithelial-Mesenchymal Transition , MicroRNAs/genetics , Phosphatidylinositol 3-Kinases/metabolism , Wnt Signaling PathwayABSTRACT
Objective:To investigate the incidence of acute kidney injury (AKI) following pancreaticoduodenectomy and related risk factors in elderly patients.Methods:The clinical data of elderly patients who underwent pancreaticoduodenectomy in Henan Provincial People′s Hospital from January 2017 to June 2020 were collected retrospectively. According to the changes of serum creatinine within 48 h or 7 days after operation, the patients were divided into AKI group and non-AKI group. The basic clinical characteristics of the two groups were compared, and the incidence of AKI was calculated. Multivariate logistic regression model was used to analyze the risk factors of postoperative AKI.Results:A total of 322 elderly patients were enrolled, with age of (67.1±5.2) years old (60-85 years old) and 186 males (57.76%). Among 322 elderly patients, there were 41 patients (12.73%) suffering from AKI following pancreaticoduodenectomy. Compared with the non-AKI group, the level of bilirubin in AKI group was higher ( Z=-2.012, P=0.044), and the level of hemoglobin in AKI group was lower ( Z=-2.111, P=0.035). Multivariate logistic regression analysis showed that increased preoperative total bilirubin ( OR=1.003, 95% CI 1.000-1.006, P=0.027) and postoperative exploratory laparotomy ( OR=3.936, 95% CI 1.071-14.460, P=0.039) were the independent influencing factors for AKI after pancreaticoduodenectomy in elderly patients. Conclusions:The incidence of AKI after pancreaticoduodenectomy in elderly patients is 12.73%. Preoperative high bilirubin and postoperative exploratory laparotomy may be the independent risk factors for AKI after pancreaticoduodenectomy in elderly patients.
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Radiomics can quantitatively analyze and process large amounts of image features from medical image data to quantify tumor heterogeneity and non-invasively evaluate tumor biological behavior. Radiomics in nuclear medicine, especially in PET is developing rapidly. This article reviews the application of radiomics in the tumor identification and prognosis evaluation, and discusses the challenges and prospects for radiomics, in order to raise the awareness of radiomics in PET.
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The aim of this study was to establish an efficient and stable mouse model of hyperuricemic nephropathy (HN) by testing different modes of administration of potassium oxonate (PO) combined with hypoxanthine (Hx). Animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guangdong Pharmaceutical University. Male C57BL/6 mice were randomly divided into a control group, a PO+Hx group (i.g.; 100 mg·kg-1·d-1 and 500 mg·kg-1·d-1, respectively), and a PO+Hx group (i.p.; 100 mg·kg-1·d-1, and 500 mg·kg-1·d-1). This HN model was induced by combination of PO and Hx administration once daily for 21 days. The results of serum biochemistry showed that the levels of serum creatinine and 24 h albuminuria were increased compared with the normal group in intragastric administration of PO combined with Hx (P < 0.05), but there was no significant difference in serum uric acid and hepatic levels of xanthine oxidase. The maximum value of serum uric acid and creatinine was 349.3 μmol·L-1 and 26.4 μmol·L-1, respectively, in mice injected with PO combined with Hx. The levels of liver xanthine oxidase and 24 h albuminuria were significantly increased in mice injected with PO combined with Hx (P < 0.01). Pathological data showed that renal tubules were dilated, the epithelial cells of renal tubules were disordered, and the production of collagen fibers, reactive oxygen species (ROS) and lipid peroxidase 4-hydroxynonenal (4-HNE) were slightly increased after intragastric administration of PO combined with Hx mice. Obvious infiltration of inflammatory cells and large area of collagen deposition, with a large amount of ROS and the lipid peroxide 4-HNE were produced in mice injected with PO combined with Hx. Western blot analysis showed that the expression of fibronectin (FN) and urate transporter 1 (URAT1) was increased after intragastric administration of PO combined with Hx in mice and further increased in mice injected with PO combined with Hx. This study demonstrates that injection with 100 mg·kg-1 potassium oxonate combined with 500 mg·kg-1 hypoxanthine establishes a stable and efficient mouse HN model.
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Objective:To investigate the inhibitory effect of brazilin on bladder cancer cells and its mechanism.Methods:Chemically synthesized brazilin was synthesized by chemical synthesis. Methyl thiazolyl tetrazolium (MTT) method was used to detect the inhibitory effect of synthetic brazilin on bladder cancer cells T24 and BIU87. Proteomic technique was used to detect the effect of brazilin on the level of protein in both cells. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot methods were used to verify the effects of brazilin on the expression of protein regulator of cytokinesis 1 (PRC1) of both cells at gene and protein level.Results:MTT method showed that brazilin significantly inhibited the proliferation of bladder cancer cells T24 and BIU87, and its half inhibitory concentration ( IC50) of T24 cell and BIU87 cell was 9.9 μg/ml and 5.1 μg/ml,respectively. Proteomic results showed that brazilin could regulate the protein expression of PRC1 in both cells, which was verified by qRT-PCR and Western blot. Conclusion:Brazilin suppresses bladder cancer cell growth possibly by downregulating PRC1.
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Objective To investigate the value of serum IgG4 level in the differential diagnosis of IgG4-related pancreatic and hepatobiliary disease (IgG4-PHD) and non-IgG4-related disease (non-IgG4-RD). Methods Clinical data were collected from 491 patients who were hospitalized and 50 individuals who underwent physical examination in Huaian No. 1 People's Hospital Affiliated to Nanjing Medical University, Subei People's Hospital, and The First Affiliated Hospital of Xuzhou Medical University from August 2014 to April 2021. The 491 patients were divided into IgG4-PHD group with 20 patients, non-IgG4-RD autoimmune disease group with 431 patients (104 patients with systemic lupus erythematosus, 79 with rheumatoid arthritis, 174 with Sjogren's syndrome, 16 with ankylosing spondylitis, 11 with scleroderma, 4 with adult-onset Still's disease, 30 with myositis, 3 with psoriasis, and 10 with primary sclerosing cholangitis), and malignant pancreatic/hepatobiliary tumor group with 40 patients, and the 50 individuals undergoing physical examination were enrolled as healthy control group. Scattering immunoturbidimetric assay was used to measure serum IgG4 concentration. The two-sample Mann-Whitney U test was used for comparison of normally distributed continuous data between groups, and the Fisher's exact test was used for comparison of categorical data between groups. The receiver operating characteristic (ROC) curve was plotted to determine the optimal cut-off value of serum IgG4 in the diagnosis of IgG4-PHD. Results The IgG4-PHD group had a significantly higher serum IgG4 level than the non-IgG4-RD autoimmune disease groups, the malignant pancreatic/hepatobiliary tumor group, and the healthy control group (all P < 0.05), and the Sjogren's syndrome group had a significantly lower serum IgG4 level than the healthy control group ( Z =2.958, P < 0.05). With serum IgG4 ≥1.35 g/L and IgG4 ≥2.01 g/L as the cut-off values, the IgG4-PHD group had a significantly higher positive rate than the non-IgG4-RD autoimmune disease group and the healthy control group (all P < 0.05). The ROC curve analysis showed that IgG4 had an area under the ROC curve of 0.980 in the differential diagnosis of IgG4-PHD and non-IgG4-RD autoimmune diseases, with a sensitivity of 100.00% and a specificity of 94.00% at the optimal cut-off value of 2.21 g/L. Conclusion Serum IgG4 level may also increase in non-IgG4-RD autoimmune diseases, while the cut-off value of 2.21 g/L can improve the differential diagnosis of IgG4-PHD and non-IgG4-RD autoimmune diseases, which requires further verification in clinical practice.
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Objective:To establish a patient-derived xenotransplantation (PDX) animal model of gastric cancer, and observe the anti-cancer effect of chemotherapeutic drugs on this model.Methods:Human gastric cancer tissues were inoculated into the subcutaneous tissues of both axillaries of NOG mice and were subcultured for 3 generations. The tumor tissues of the third-generation NOG mice were selected and inoculated into the subcutaneous tissues of left axillary of 21 severe combined immunodeficiency-non-obese diabetes mellitus (SCID-NOD) mice to establish PDX mouse model of gastric cancer. The inoculated mice were divided into control group (mice received only 0.9% sodium chloride injection), oxaliplatin group, cisplatin group, paclitaxel group, fluorouracil group, tegafur, gimeracil and oteracil porassium capsules group and capecitabine group, with 3 mice in each group, and the corresponding drugs were given. The mice survival status, tumor volume and tumor weight at different times were recorded. Mice were sacrificed on the 61st day of administration, and the tumor inhibition effects of 6 kinds of chemotherapy drugs on the PDX model of gastric cancer were evaluated.Results:After being subcultured for 3 generations, the stability of tumor transmission in PDX animal model of gastric cancer was improved, and the homogeneity of tumor growth was good at the initial stage. At the early stage of administration, the model was more sensitive to oxaliplatin, fluorouracil and capecitabine, and the tumor growth inhibition (TGI) values on the 31st day were 63.37%, 52.11% and 78.48%, at the end of administration, the model had the best sensitivity to capecitabine with a TGI value of 59.22% and a tumor inhibition rate of 58.65% on the 61st day. The TGI curve after administration showed that paclitaxel had no obvious anti-tumor effect, cisplatin had the worst anti-tumor effect, and the model had poor tolerance to tegafur, gimeracil and oteracil porassium capsules.Conclusion:The PDX animal model of gastric cancer is successfully established, and capecitabine has the best tumor suppressive effect on this model.
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Objective:To investigate the inhibiting effect of Sufuning Lotion (SFN) on bladder carcinoma T24 cells.Methods:Trypan blue exclusion test was performed to observe the killing effect of 2 mg/ml SFN at different time points (20, 40, 60, 80, 100 min) on human bladder carcinoma T24 cells; the inhibiting effect of SFN with different concentrations (8.0, 12.0, 18.0, 27.0, 40.5 μg/ml) for 48 h on proliferation of T24 cells was assessed by using methyl thiazolyl tetrazolium (MTT) assay. The half inhibitory concentration ( IC50) was identified. T24 cells were treated with IC50 SFN for 24, 48, 72 h, and then the change of proliferation inhibition rate of T24 cells was detected. The nude mice subcutaneous model (30 mice) and intraperitoneal tumor xenograft model (30 mice) were prepared according to T24 cells inoculated method. After inoculation for 24 h, both animal models were divided into 5 groups with 6 animals in each group based on the random number method, including the control group (0.9% NaCl solution), the SFN 200 mg/kg group, the SFN 300 mg/kg group, the SFN 400 mg/kg group and the mitomycin group, and then the control group and three SFN groups were intraperitoneally injected for 6 d, while the mitomycin 1 mg/kg group was injected with 1 mg/kg mitomycin every 5 d for once, 2 times in total. The transplantable tumor volume of subcutaneous tumor xenograft model was measured per week and the mice were sacrificed after 4 weeks. Tumor tissues were taken out to measure the tumor weight and tumor growth inhibition ratio was also evaluated. The survival time of nude mice in intraperitoneal tumor xenograft model was recorded so as to calculate the life extension rate. Results:Trypan blue exclusion test showed that after the function of 2 mg/ml SFN for 20, 40, 60, 80, 100 min, the cell death rate was (17.83±1.56)%, (48.95±1.34)%, (67.46±1.44)%, (75.48±2.12)%, (89.41±1.35)%, respectively, and the difference was statistically significant ( F = 1 213.264, P < 0.01). MTT assay showed that SFN inhibited the proliferation of T24 cells in a concentration-dependent and time-dependent manner, and the IC50 of cell proliferation at 48 h was (14.36±0.35) μg/ml. After the function of 14.36 μg/ml SFN for 24, 48, 72 h, the proliferation inhibitory rate of T24 cells was (39.5±0.9)%, (50.6±0.7)%, (71.5±1.0)%, respectively, and differences was statistically significant ( F = 1 044.206, P < 0.01). After the nude mice was inoculated with T24 cells for 4 weeks, the tumor volume and tumor weight in the SFN 200 mg/kg group, the SFN 300 mg/kg group, the SFN 400 mg/kg group and the mitomycin group were lower than those in the control group [the tumor volume: (0.925±0.136) cm 3, (0.833±0.171) cm 3, (0.652±0.117) cm 3, (0.482± 0.120) cm 3 vs. (1.231±0.210) cm 3, respectively; the tumor weight: (1.56±0.20) g, (1.42±0.21) g, (1.19±0.22) g, (0.97±0.16) g vs. (1.98±0.30) g], and differences were statistically significant ( F = 20.153, P < 0.01; F = 17.325, P < 0.01); there were no significant differences in the tumor volume and weight between the SFN 400 mg/kg group and the mitomycin group ( t = 1.898, P = 0.069; t = 1.739, P = 0.094), the inhibition rate of subcutaneous tumor xenograft model was 20.94%, 28.28%, 39.66%, 51.14%, respectively in the SFN 200 mg/kg group, the SFN 300 mg/kg group, the SFN 400 mg/kg group and the mitomycin group. The survival time of intraperitoneal nude mice in the SFN groups and the mitomycin group was prolonged compared with that in the control group [(32.7±3.2) d, (34.0±4.5) d, (34.3±2.3) d, (35.3±2.0) d vs. (21.7±4.8) d], and there was a statistically significant difference ( F = 15.179, P < 0.01), the life extension ratio was 50.76%, 56.90%, 58.42%, 63.04%, respectively. Conclusion:SFN can inhibit the proliferation of T24 cells, and it has an anti-tumor effect on the T24-bearing nude mice.
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Objective:To establish a rat model of neurogenic bladder and analyze the changes in kidney morphology and function and the expression of proteins in AngiotensinⅡ(AngⅡ)/transforming growth factor β1 (TGF-β1)/Smads pathway.Methods:Sprague-Dawley rats were randomly divided into experimental group (spinal nerve amputation, n=36) and control group (sham operation, n=12). At 6, 12, and 24 weeks, the bladder compliance was measured by cystometry, the kidney morphology was detected by B-ultrasound, blood urea nitrogen (BUN) and serum creatinine (Scr) in blood samples were examined, the kidney pathological changes were detected by Masson and HE staining, the distribution of AngⅡ/TGF-β1/Smads pathway proteins was analyzed by immunohistochemisty, and the protein expressions in kidney were detected by Western blotting. Results:Urodynamics showed that the basic bladder pressure in experimental group was higher than that in control group. B-ultrasound showed that compared with the control group, the diameter of the renal pelvis of the rats with nerve dissection gradually increased ( P<0.05), and the hydronephrosis was gradually obvious. Compared with the control group, the BUN and Scr in experimental group gradually increased (both P<0.01). Masson and HE staining showed that compared with the control group, the collagen expression and renal tubulointerstitial scores in experimental group were gradually increased (both P<0.01). Immunohistochemisty showed that compared with the control group, in experimental group the expression of angiotensinⅡ receptor type 1 (AT1), TGF-β receptor 1(TGF-βR1), phosphorylated Smad2 gradually increased (all P<0.01), the pathway inhibitor Smad6 gradually decreased ( P<0.01), and the distribution of each protein in kidney was consistent. Western blotting showed a corresponding expression trend with immunohistochemisty. Conclusions:In neurogenic bladder caused by bilateral spinal nerve amputation, due to bladder dysfunction, increased bladder pressure induces hydronephrosis, destruction of the nephron structure, activation of AngⅡ/TGF-β1/Smads pathway, and renal fibrosis. This method is effective and has clinical similarities, laying a foundation for exploring neurogenic bladder treatment.
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Objective:To analyze the influencing factors of death in patients with acute respiratory distress syndrome (ARDS) combined with acute kidney injury (AKI) in intensive care unit (ICU) after continuous renal replacement therapy (CRRT).Methods:The demographic and clinical data of ICU patients with ARDS combined with AKI after CRRT at Henan Provincial People's Hospital from January 1, 2018 to December 31, 2018 were collected. According to the final treatment results of this hospitalization, the patients were divided into death group and survival group. Survival was defined as the improved patient's condition and hospital discharge. Death was defined as the patient's death during the ICU hospitalization or confirmed death after abandoning treatment and automatically being discharged from the hospital in the follow-up. The basic clinical characteristics and CRRT status between the two groups were compared. Multivariate logistic regression method was used to analyze the influencing factors of death in patients.Results:A total of 132 patients were enrolled, of which 90 patients (68.2%) died, with 84 males (63.6%) and median age of 59(45, 73) years. Compared with the survival group, the death group had higher age, proportion of malignant tumors, sequential organ failure assessment (SOFA) score, number of organ dysfunction and proportion of positive balance of fluid accumulation at 72 hours, longer time from entering ICU to CRRT, and lower mean arterial pressure (minimum value) and oxygenation index (all P<0.05). Multivariate logistic regression analysis results showed that the age≥60 years old ( OR=4.382, 95% CI 1.543-12.440, P=0.006), large number of organ dysfunction ( OR=1.863, 95% CI 1.109-3.130, P=0.019), high SOFA score ( OR=1.231, 95% CI 1.067-1.420, P=0.004) and long time from ICU admission to CRRT ( OR=1.224, 95% CI 1.033~1.451, P=0.020) were independent influencing factors of death in patients with ARDS combined with AKI after CRRT, and high oxygenation index ( OR=0.992, 95% CI 0.986-0.998, P=0.010) was an independent protective factor for patients' prognosis. Conclusions:The mortality of patients with ARDS combined with AKI after CRRT is still high. The age≥60 years old, large number of organ dysfunction, high SOFA score and long time from ICU admission to CRRT are independent influencing factors for death, and high oxygenation index is an independent protective factor for prognosis in patients with ARDS combined with AKI after CRRT.
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Objective:To investigate the relationship between monocyte/high-density lipoprotein ratio (MHR) and clinical parameters and the prognosis of patients with chronic kidney disease (CKD).Methods:Clinical data were collected of CKD patients who were diagnosed and followed up regularly in Henan Provincial People's Hospital from January 1, 2017 to June 30, 2020. According to the median baseline MHR of the selected patients, they were divided into two groups: low-level MHR group (MHR≤0.347 8) and high-level MHR group (MHR>0.347 8). The patients were regularly followed up for 3-42 months, the renal adverse prognostic events were defined as serum creatinine doubled, estimated glomerular filtration rate (eGFR) reduced to at least 50% of the original, new entry into end-stage renal disease (ESRD), starting renal replacement therapy, death due to renal or cardiovascular events. The Kaplan-Meier method was used to compare the differences in survival rates between the two groups, and Cox regression analysis method was used to explore the influencing factors of renal adverse prognosis in CKD patients. Stratified analysis was used to find special factors that might affect the relationship between MHR and renal adverse prognosis in CKD patients.Results:A total of 405 patients were included in this study. Their age was (49.77±14.82) years old. Body mass index was (25.18±4.22) kg/m 2. Women accounted for 30.62%(124/405). The proportion of patients with smoking, drinking, hypertension and diabetes was 39.51%(160/405), 35.06%(142/405), 73.33%(297/405) and 38.27%(155/405), respectively. Compared with the low-level MHR group ( n=202), the high-level MHR group ( n=203) had more people in late CKD, males, and hypertension (all P<0.01), and body mass index, white blood cells, monocytes, serum creatinine, serum uric acid, serum urea nitrogen, retinol binding protein, cystatin C, blood phosphorus were higher (all P<0.05), while hemoglobin, high density lipoprotein and eGFR were lower (all P<0.05). Spearman rank correlation results show that MHR level was positively correlated with white blood cells, serum creatinine, serum uric acid, serum urea nitrogen, retinol-binding protein, cystatin C, serum phosphorus (all P<0.01), and negatively correlated with hemoglobin and eGFR (both P<0.01). The median follow-up time was 8(4, 16) months. To the end of the follow-up, 113 patients (27.90%) had renal adverse prognostic events. Kaplan-Meier survival analysis results showed that the renal cumulative survival rate of the high-level MHR group was lower than that of the low-level MHR group ( χ2=8.277, P=0.004). Multivariate Cox regression analysis showed that high MHR level was an independent influencing factor for poor renal prognosis in CKD patients ( HR=1.628, 95% CI 1.050-2.523, P=0.029). Stratified analysis showed that, without hypertension, MHR had a more significant effect on the prognosis of the kidneys ( HR=3.414, 95% CI 1.091-10.686, P for interaction=0.001). Conclusions:The level of MHR is related to the severity and poor renal prognosis of CKD, and the high MHR level is an independent predictor for poor renal prognosis in CKD patients.
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Netrin-1, an axon guidance factor, and its receptor UNC5B play important roles in axonal development and angiogenesis. This study examined netrin-1 and UNC5B expression in kidneys with diabetic kidney disease (DKD) and investigated their roles in angiogenesis. Netrin-1 and UNC5B were upregulated in streptozotocininduced DKD Wistar rats, and their expression was compared with that in healthy controls. However, exogenous netrin-1 in UNC5B-depleted human renal glomerular endothelial cells (HRGECs) inhibited cell migration and tubulogenesis. This effect was likely associated with SRC pathway deactivation. Netrin-1 treatment also eliminated the pro-angiogenic effects of exogenous VEGF-165 on UNC5B-silenced HRGECs. These results indicate that UNC5B antagonizes netrin-1 and that UNC5B upregulation contributes partly to enhancing angiogenesis in DKD. Therefore, introducing exogenous netrin-1 and depleting endogenous UNC5B are potential strategies for reducing the incidence of early angiogenesis and mitigating kidney injury in DKD.
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Objective:To assess the value of urine heat-shock protein-70 (HSP-70) in the early diagnosis of acute kidney injury (AKI) after cardiac cardiopulmonary bypass (CPB).Methods:Patients with cardiopulmonary bypass from May 2018 to July 2018 in Henan Provincial People's Hospital were enrolled as subjects. Urine samples were collected before and after cardiopulmonary bypass at 0 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h. Patients were divided into AKI group and non-AKI group according to the Kidney Disease: Improving Global Outcomes Guide. Urinary HSP-70, tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) were detected by enzyme-linked immunosorbent assay (ELISA) and urine neutrophil gelatinase-associated lipocalin (NGAL) was determined by immunoturbidimetry. The receiver operating characteristic (ROC) curve was plotted to calculate the critical value, sensitivity and specificity of urine HSP-70, [TIMP-2]×[IGFBP7] and NGAL for the diagnosis of postoperative AKI after CPB.Results:A total of 45 patients were enrolled in the study. There were 24 cases in AKI group and 21 cases in non-AKI group. The level of urinary HSP-70, [TIMP-2]×[IGFBP7] and NGAL in AKI group were significantly higher than in the non-AKI group at each postoperative time point, with statistically significant differences (all P<0.05). The level of urinary HSP-70 in AKI group peaked at 2 h after CPB, which was significantly earlier than the peak time of urine [TIMP-2]×[IGFBP7] and urine NGAL (12 h after CBP and 4 h after CBP, respectively). Urinary HSP-70≥2.1 μg/L could predict postoperative AKI of CPB at 2 h after CPB, with the area under the curve ( AUC) of 1.00, the sensitivity of 100.0% and the specificity of 100.0%. Urinary [TIMP-2]×[IGFBP7]>19.1 μg 2/L 2 could predict postoperative AKI of CPB at 12 h after CPB with the AUC of 0.94, the sensitivity of 87.5%, and the specificity of 100.0%. Urinary NGAL>27.4 μg/L could predict postoperative AKI of CPB at 4 h after CPB with the AUC of 0.95, the sensitivity of 95.8%, and the specificity of 85.7%. The positive predictive value of urine HSP-70≥2.1 μg/L at 2 h after CPB was 100.0%, and the negative predictive value was 100.0%. Conclusions:The level of urinary HSP-70 increases earlier than that of urinary [TIMP-2]×[IGFBP7] and NGAL in patients with AKI after CPB. Clinical monitoring of urinary HSP-70 level contributes to early diagnosis of AKI.
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Objective:To evaluate the safety and feasibility of intranodal lymphangiography combined thoracic duct embolization in the treatment of chylous leakage.Methods:The clinical data of ten patients with chylous leakage from July to December 2019 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. There were 6 cases of chylothorax, 1 case of chylous ascites, and 3 cases of chylothorax combined with chylous ascites, respectively. Conservative treatment was invalid in all cases. The locations of cisterna chyli and thoracic duct were defined by percutaneous puncture intranodal lymphangiography. Then the percutaneous transabdominal puncture of cisterna chyli was performed and the microcatheter was inducted. The location of fistula was visualized by thoracic duct lymphangiography, and the embolization was performed by microcoils combined tissue adhesive agents. The post-operative curative effect and complications were recorded.Results:One patient did not receive thoracic duct embolization because it was failed to visualize cisterna chyli by intranodal lymphatic angiography; thoracic duct embolization was successfully performed in the other 9 patients after chylous leakage fistula was located. Percutaneous transabdominal puncture of cisterna chyli was successfully accomplished in 8 patients. As for the other patient, after repeated failure of puncture, fluoroscopy-guided retrograde puncture at the proximal thoracic duct was performed successfully. After the operation, the drain output was completely disappeared within 3 to 7 days in 8 patients, and decreased down to 120 ml/d in 1 patient. Mild abdominal hemorrhage was found in 1 patient after thoracic duct embolization, without any treatment. No serious complications was found in all cases.Conclusion:Intranodal lymphangiography and thoracic catheter embolization is safe and effective in the treatment of chylous leakage, with a low complication rate.