Hyperuricemic nephropathy （HN）， a secondary renal damage common in clinical practice， is characterized by early concealing and continuous progression. The understanding of HN in traditional Chinese medicine （TCM） is from a macroscopic perspective. According to the TCM theory， HN is caused by the combination of external pathogens and internal injuries， with the main pathogenesis being root deficiency combined with superficial excess and deficiency-excess in complexity. In western medicine， the understanding of HN is from the microscopic perspective， which holds that the occurrence of HN is the result of inflammation， oxidative stress， renin-angiotensin-aldosterone system （RAAS） activation， and metabolic abnormalities. The TCM syndromes of HN include internal dampness and heat， obstruction in dampness and turbidity， deficiency of spleen and kidney， and deficiency of kidney yin. Accordingly， the prescriptions should clear heat and dampness， remove dampness and turbidity， tonify spleen and kidney， and nourish kidney yin， respectively. In addition to TCM prescriptions， single herbal medicines and their extracts， Chinese patent medicines， and external applications of Chinese medicines have played a significant role in the treatment of HN， promoting the application of TCM in the treatment of HN. Moreover， the integrated traditional Chinese and western medicine has also played a role in the treatment of HN， enriching the treatment schemes of HN. Different from common kidney diseases such as acute and chronic glomerulonephritis and nephrotic syndrome， HN with particularity should be carefully differentiated in clinical practice. This article systematically summarizes the research progress in the treatment of traditional Chinese medicine and integrated traditional Chinese and western medicine on hyperuricemic nephropathy with TCM and integrated traditional Chinese and western medicine， aiming to enrich the system and theory of HN treatment and further guide the clinical practice.

【Objective】 To explore the application value of free prostate specific antigen density(fPSAD) based on rectal ultrasound in the prediction of prostate biopsy results. 【Methods】 Data of 578 patients undergoing transrectal ultrasound guided prostate biopsy during Jan.2014 and Jul.2021 were retrospectively analyzed, including prostate specific antigen(PSA) level, free prostate specific antigen(fPSA) level, fPSA/total prostate specific antigen(tPSA), prostate specific antigen density(PSAD), combined prostate specific antigen density(cPSAD), fPSAD, prostate volume and other clinical parameters. 【Results】 There were 253 cases of prostate cancer and 325 cases of prostatic hyperplasia. The positive puncture rate was 43.8%. The critical value of fPSAD was 0.05, the corresponding area under receiver operating characteristic (ROC) curve was 0.830, and the Yoeden index was 0.539. The sensitivity, specificity, diagnosis accordance rate and Kappa value of fPSAD to predict prostate cancer were 0.76, 0.77, 76.7% and 0.529, respectively. Compared with PSA, fPSA/tPSA and PSAD, PSA had the highest sensitivity (92.5%), fPSAD had the highest specificity (77.2%), and fPSAD had the highest diagnostic accordance rate (76.7%). 【Conclusion】 When transrectal prostate volume measurement is used to predict prostate cancer, fPSAD has relatively high specificity and diagnosis accordance rate, which is obviously better than using PSA, fPSA/tPSA ratio and PSAD alone in the differential diagnosis and prediction of prostate cancer and prostatic hyperplasia.

The aim of this study was to construct a recombinant adenovirus expressing extracellular domain gene of human epidermal growth factor receptor variant Ⅲ (EGFRvIII ECD), and to prepare single domain antibody targeting EGFRvIII ECD by immunizing camels and constructing phage display antibody library. Total RNA was extracted from human prostate cancer cell line PC-3 cells and reversely transcribed into cDNA. EGFRvIII ECD gene was amplified using cDNA as template, and ligated into pAdTrack-CMV plasmid vector and transformed into E. coli BJ5183 competent cells containing pAdEasy-1 plasmid for homologous recombination. The recombinant adenovirus expressing EGFRvIII ECD was obtained through transfecting the plasmid into HEK293A cells. The recombinant adenovirus was used to immunize Bactrian camel to construct EGFRvIII ECD specific single domain antibody library. The single domain antibody was obtained by screening the library with EGFRvIII protein and the antibody was expressed, purified and identified. The results showed that recombinant adenovirus expressing EGFRvIII ECD was obtained. The capacity of EGFRvIII specific phage single domain antibody library was 1.4×10⁹. After three rounds of enrichment and screening, thirty-one positive clones binding to EGFRvIII ECD were obtained by phage-ELISA, and the recombinant single domain antibody E14 with highest OD₄₅₀ value was expressed and purified. The recombinant E14 antibody can react with EGFRvIII ECD with high affinity in ELISA assessment. The results indicated that the EGFRvIII specific single domain antibody library with high capacity and diversity was constructed and the single domain antibody with binding activity to EGFRvIII was obtained by screening the library. This study may facilitate the diagnosis and treatment of EGFRvIII targeted malignant tumors in the future.
Adenoviridae/genetics* ; DNA, Complementary ; ErbB Receptors ; Escherichia coli/genetics* ; Genetic Vectors/genetics* ; Humans ; RNA ; Recombinant Proteins/metabolism* ; Single-Domain Antibodies

Objective:To investigate epithelial-mesenchymal transition and to explore the effects of mitochondrial dysfunction and increased expression of TGF-β1 pathway on epithelial-mesenchymal transition (EMT) in pancreatic adenocarcinoma after X-ray irradiation.Methods:Split-dose irradiations of total 40 Gy (2 Gy × 20 and 4 Gy × 10) of 6 MV X-rays were performed on PATU1 988 t cells. The migration of the cells were examined through transwell filter chambers. Real-time PCR was adopted to detect the expression of EMT-related factors E-cadherin, Vimentin, N-cadherin, and MMPs (MMP2 and MMP9), critical subunits of mitochondrial complex I, and TGF-β1. The expression of EMT-related factors and content of TGF-β1 was detected after carbonylcyanide-m-chlorophenylhydrazone(CCCP) treatment. Meanwhile, the migration potential of pancreatic cells was detected after small interfering RNA (siRNA) knockdown of the expression of TGF-β1.Results:After irradiation, the migration capacities of the cancer cells increased ( t=21.90, 35.64, P<0.05). The expression of N-cadherin ( t=4.42, 4.77, P<0.05), Vimentin ( t=4.57, 3.02, P<0.05), MMP2 ( t=7.27, 26.08, P<0.05), and MMP9 ( t=13.26, 7.29, P<0.05) all increased, while the expression of E-cadherin deceased ( t=8.37, 6.77, P<0.05). The expression of TGF-β1 ( t=90.49, 35.17, P<0.05) increased. The expression of TGF-β1 decreased with small interfering RNA, which paralleled the inhibition of the epithelial-mesenchymal transition and migration ( t=38.66, 11.54, P<0.05). Mitochondrial dysfunction was reflected by the decline in the membrane potential ( t=6.94, 29.71, P<0.05) and complex-related subunits. The expression of TGF-β1 ( t=47.93, P<0.05) and EMT-related factors further increased after mitochondrial function was destroyed ( t=16.51, P<0.05). Conclusions:Radiation-induced mitochondrial dysfunction can increase the expression of TGF-β1, which promotes epithelial-mesenchymal transition, and result in the migration of pancreatic cancer cell line.

Objective:To investigate the expression of Pyruvate dehydrogenase kinase 1(PDK1), phosphorylated Pyruvate dehydrogenase (p-PDH) and Pyruvate kinase isozyme type M2 (PKM2) based on Warburg effect pathway in cervical cancer tissues, and explore the roles of these molecules on prognosis and recurrence after postoperative radiation.Methods:The expressions of PDK1, p-PDH and PKM2 in primary tissues of 102 patients with cervical cancer were detected by immunohistochemistry, including 63 patients receiving postoperative radiation. The expression of the three molecules on prognosis and the efficacy of postoperative radiation on cervical cancer were analyzed separately and corporately.The level of mRNA were verified by using the 300 patients from GEO database. Kaplan-Meier method and COX proportional hazards regression model were used for univariate and multivariate analysis.Results:High expression of PDK1 and all the three indicators (PDK1 high/p-PDH high/PKM2 high) were positively correlated with pelvic lymphnode metastasis ( χ2=10.890, 7.407, P<0.05). PDK1 high/p-PDH high/PKM2 high, Federation International of Gynecology and Obstetrics (FIGO) staging, pelvic lymph node metastasis and postoperative radiation could affect the overall survival (OS) and disease-free survival (DFS) ( P<0.05). Multivariate analysis showed that PDK1 high /PDH high/PKM2 high, FIGO staging and postoperative radiation were the independent prognosis factors for OS and DFS( P<0.05). The verification result of the GEO dataset showed that PDK1 high/PDH high/PKM2 high was the risk factor for DFS( P<0.05). Pathological type, pelvic lymph node metastasis and PDK1 high/p-PDH high/PKM2 high could affect the DFS of those patients with postoperative radiation ( P<0.05). In addition, the multivariate analysis showed that pathological type and PDK1 high /p-PDH high/PKM2 high were the independent prognosis factors for DFS( P<0.05). Conclusions:The patients of PDK1 high /p-PDH high/PKM2 high phenotype have poor prognosis and DFS with postoperative radiation, which may be a high-risk group with poor prognosis and high recurrence rate after postoperative radiotherapy of stageⅠ-Ⅱ B cervical cancer.This study provides a novel strategy for stratified treatment of cervical cancer.

Objective To investigate the expression of microrchidia 2(MORC2) in glioblastoma patients and to evaluate its prognostic value of MORC2 expression combined with IDH1 mutation status for chemoradiotherapy efficacy and new molecular subtype.Methods The expression level of MORC2 in 45 glioblastoma tissues was measured by immunohistochemical staining and its correlation with clinicopathological characteristics and clinical prognosis after chemoradiotherapy was analyzed.Further more,the prognostic values of the expression of MORC2 combined with the status of IDH1 were assessed in a glioblastoma CGGA mRNA dataset.Results High expression of MORC2 was observed in 76％ of glioblastoma patients,which was negatively correlated with overall survival (HR=2.928,95％CI:1.582-5.418,P=0.002;recurrence-free survival (HR=2.204,95％CI:1.186-4.095,P=0.022).Moreover,according to the prognosis value of MORC2 expression and IDH1 mutation status,glioblastoma patients were divided into 3 molecular subtypes.Patients with the subtype of IDH1mt/MORC2low obtained the best clinical prognosis with a median survival of 22 months (95％CI:13.98-30.02),whereas those with the subtype of IDH1wt/MORC2high obtained the worst clinical prognosis with a median survival of 5.63 months (95％CI:3.92-7.34,HR=4.15,95％CI:3.92-7.34,P=0.002).Among IDH1wt glioblastoma patients,MORC2high patients had worse clinical prognosis compared with MORC2low counterparts,prompting that IDH1wt/ MORC2high glioblastoma tissues yielded higher capability of DNA injury repairing and resistance to chemoradiotherapy.Conclusions The high expression of MORC2 can be used as a potential indicator of poor prognosis of glioblastoma patients after chemoradiotherapy.IDH 1 mutation status combined with MORC2 expression can establish a novel molecular subtyping,which provide evidence for stratified therapy for glioblastoma patients.

Objective To investigate the effect of fat-specific protein 27 (Fsp27) gene on primary hepatic stellate cells (HSCs) in vitro.Methods Rt-PCR was used to detect the expression of Fsp27 gene in primary and activated HSCs.The lentivirus carrying Fsp27 was constructed and transfected into primary HSCs.Effect of Fsp27 gene on proliferation of HSCs was tested by CCK-8 colorimetry.Detection of HSCs α-actin (oα-SMA) expression was tested by Western blotting.Effect of Fsp27 gene on expression of fibrosisrelated genes in HSCs were tested by Real-time quantitative PCR.Results The difference of Fsp27 gene between primary HSCs and activiated HSCs was significant (Fsp27 mRNA:2 700 ± 500,5 ± 2,t =124.27,P ＜ 0.05).After coculture for 72h,the proliferation and activation of HSCs was inhibited by Fsp27 (48 h:31.5±1.3,6.1±0.1,t=17.35,P＜0.05;72h:36.2±2.2,6.2±0.1,t=21.94,P＜0.05).Fsp27 can enhance the expression of MMP-2 gene (0.48 ± 0.02,0.85 ± 0.14,1.63 ± 0.21,F =41.56,P ＜ 0.05) and down-regulate the expression of TGF-[1 gene in activiated HSCs (3.2 ± 0.17,2.0 ± 0.3,1.7 ± 0.2,F =21.52,P ＜ 0.05).Conclusion Fsp27 gene can inhibit the proliferation and activation of primary HSCs.Fsp27 can regulate the expression of fibrosis related gene.Fsp27 may play an important role in maintenance the quiescent phenotype of HSCs.

Objective To explore the evaluation value of dynamic monitoring of neutrophil/lymphocyte ratio(NLR)in severity of illness and prognosis of bacterial sepsis.Methods Clinical data and laboratory index of 72 cases of patients with bacterial sepsis in ICU of Yangpu Hospital Affiliated to Tongji University were retrospectively analyzed.According to the severity of illness,patients were divided into sepsis group(n=20),severe sepsis group(n=30)and septic shock group(n=22).According to the mortality within 28 d,patients were divided into survival group(n=47),death group(n=25).The 0 h NLR,48 h NLR and change rate of NLR between two groups were compared,and the influence factors of prognosis were analyzed.Results With the increase of severity of illness,the time of mechanical ventilation was shortened((8.8±1.9)d,(4.6±0.6)d,(3.9±0.4)d),and PLT((146.4±45.8)×109/L,(110.6±41.3)×109/L,(102.5±38.6)×109/L),NLR rate(0.61±0.26,0.26±0.11,0.22±0.09)were decreased significantly,APEACHE Ⅱ score,CRP,PCT,0 h NLR,48 h NLR were increased obviously((18.5±2.3)points,(20.4±3.6)points,(23.1±3.9)points;(72.6±10.4)mg/L,(78.2±11.6)mg/L,(85.2±12.5)mg/L;(1.5±0.4)μg/L,(2.3±0.6)μg/L,(2.7±0.9)μg/L;11.3±2.6,14.2±3.4,15.7±3.5;3.4±0.9,9.7±2.4,11.2±2.6),the differences were statistically significant(P＜0.05).Compared with death group,the time of mechanical ventilation in survival group was prolonged((4.1±0.3)d vs.(8.7±1.4)d),APEACHE Ⅱ score,CRP,PCT,0 h NLR,48 h NLR were decreased obviously((21.4±3.5)points vs.(18.3±2.6)points,(78.2±11.6)mg/L vs.(71.5±10.8)mg/L,(2.5±0.7)μg/L vs.(1.4±0.6)μg/L,(15.0±3.3)vs.(11.6±2.4),(10.5±2.8)vs.(3.2±0.8)),and PLT,NLR rate were increased significantly((106.5±41.5)×109/L vs.(148.4±50.8)×109/L,0.24±0.10 vs.0.65±0.24),the differences were statistically significant(t=16.18,4.26,2.44,6.99,5.01,16.73,3.54,8.15,P＜0.05).Multivariate logistic regression analysis showed that APEACHE Ⅱ score,0 h NLR were the independent risk factors of death in patients with bacterial sepsis(OR=3.99,3.01,95％CI:1.65-2.38,1.99-4.54,P＜0.05),and NLR rate was independent protection factor(OR=0.95,95％CI:0.91-0.97,P＜0.05).Conclusion Dynamic monitoring of peripheral blood NLR can help to judge the prognosis and severity of illness of patients with bacterial sepsis,and NLR before treatment and change rate of NLR are an independent predictors of death.

Objective To analyze and discuss the application effect of Fiberoptic bronchoscopic sputum aspiration combined with bronchoalveolar lavage on the treatment of ventilator associated pneumonia. Methods In our hospital from January 2015 to February 201684 cases with ventilator-associated pneumonia were, randomly divided into the observation group and the control group. The two groups were received the same conventional treatment, at this basis, the observation group were given fiber bronchoscope sputum and bronchoalveolar lavage. The effect in the two groups a was compared. Results The mechanical ventilation time, hospitalization expenses, the total effective rate in the observation group were significantly better than those in the control group , the differences were statistically significant (P<0.05). Conclusion On the basis of routine treatment, fiberoptic bronchoscopy and bronchoalveolar lavage are used on the treatment of ventilator-associated pneumonia, which can further improve the treatment effect and save the cost of treatment.

OBJECTIVE To analyze the effect of postaural injection in treating SNHL and the influence on ROS,sVCAM-1 levels.METHODS 242 low frequency descent sensorineural hearing loss patients from Jan.2010 to Jul.2016 in our hospital were selected as the research sbjects.They were randomly divided into two groups(n=121).All patients were treated with ginkgo biloba extract intravenous drip.The control group was treated with Methylprednisolone intravenous drip,while the observation group was treated with postaural injection of Methylprednisolone.The clinical effects between the two groups were compared after 14 days of treatment.The ABR result,serum ROS,sVCAM-1 levels were also copmpared before and after treatment.RESULTS The effective rates of 2 groups were 82.64％,61.16％ respectively,which indicated significant difference (P＜0.05).The Ⅰ and Ⅴ waves of observation group were decreased,and they was significantly lower than that of the control group(P＜0.05),the R-R interval between Ⅰ and Ⅴ waves of the 2 groups showed no significant difference (P＞0.05).After treatment,the serum ROS level of 2 groups were (0.66 ± 0.38) ng/ml,(2.31± 1.12) ng/ml respectively,the sVCAM-1 level of two groups were (230.5 ±26.4) ng/ml,(312.6 ±47.2) ng/ml respectively,the observation group was significantly lower than that of the control group (t=10.985,11.953,P＜0.05).CONCLUSION Methylprednisolone can improve the clinical effect in treating low frequency descent SNHLby improving the concentration of drugs in ear and increasing the activity of Na+/K+-ATP enzyme in blood vessel;It can also decrease ROS and sVCAM-1 level,alleviate oxidative stress,reduce vascular endothelial damage,which is worthy of recommendation.