Reactive oxygen species(ROS) resulting from oxidative stress plays a significant role in the pathogenesis of diabetic nephropathy.It induces cell apoptosis and accelerates the development and progression of diabetic nephropathy through mitochondrial activation,DNA oxidative injury and influence on gene expression.Reducing ROS formation and blocking the pathway of cell apoptosis activated by ROS may become a new target in the treatment of diabetic nephropathy.

Objective To investigate the mechanism of the kidney injure in the newborn rats with endotoxemia.Methods Eighty Wistar rats aged 7 days were randomly divided into 2 groups:control group (intraperitoneal injection of saline of 0.1 ml;n = 40),lipopolysaccharide(LPS) group(intraperitoneal injection of LPS of 5 mg/kg;n =40).The rats in either group were killed at 1 h,4 h,8 h and 12 hours after intraperitoneal injection,respectively.The expressions of NF-κB and TGF-β1 in the kidney were detected by using the immunohistochemical assay.Renal ultrastructural changes was observed with a CM100 Philips electron microscope.Results The NF-κB in control group had no expression.NF-κB in LPS group mainly expressed in the renal tubular epithelial cell,increased at 1 h after test and peaked at 8 h,and slightly descended at 12 h.The expression of TGF-β1 in control group was slight,and had not show significant difference from control group at 1 h,4 h and 8 h,but significantly higher than that in control group at 12 h.In LPS group,newborn rat renal glomerular basement membrane was complete,part epithelial cell foot processes were fused and renal tubules epithelial cell mild mitochondria vacuolization was found at 4 h.Renal glomeruli epithelial cell foot processes obvious confluenced,quantities of mesangial cells mitochondria vacuole,and renal tubules epithelial cell mitochondria expanded to bubbles at 12 h.Conclusion The NF-κB involves in the pathogenesis of kidney damage induced by endotoxemia,but TGF-β1 may help to repair the damaged kidney,and may repress the production of NF-κB.

Objective To study the relationship between the IgG antibody titer, the concentration of IgG subclasses in group O maternal sera and hemolytic disease of newborn. Methods By means of blood group serology assay, IgG antibody titers in 317 pregnant women who had incompatible blood group with their husbands was measured. The concentration of IgG subclasses were measured in HDN infants and their mothers, healthy pregnant women and healthy infants by ELISA. Results 1) Among 317 maternal sera, 153 cases (48.3%) were found to have IgG antibody titers higher than 1∶64, with anti-A and anti-B in 89 and 64 cases, respectively. Seventy-one (22.4%) newborns suffered from ABO-HDN, with 46 anti-A and 25 anti-B; 2) With increased numbers of pregnancy, the proportions women with greater than 1∶64 IgG antibody increased, and there was significant difference between those with one pregnancy and those with more than one pregnancies; 3) The levels of IgG antibody in HDN infants and their mothers were higher than those in control group, and IgG1 was the predominant subclass. Meanwhile, the proportion of IgG1 in infants was higher than in pregnant women. Conclusion To some couples of ABO incompatibility, IgG antibody titer and IgG subclasses should be tested in pregnant women. The incidence of HDN increases with increased antibody titers. The severity of HDN correlates positively with the concentration of IgG1 in maternal sera.

Objective To explore the effect of melatonin on mitochondria in streptozotocin (STZ)-induced diabetic rats and its potential mechanism. Methods The diabetic rat models were induced by intraperitoneal injection of STZ, and the diabetic rats were randomly divided into two groups: diabetes mellitus group (DM group) and melatonin-treated group (DM± MT group). The normal non-diabetic rats were served as control group. Mitochondrial membrane potential and mitochondrial swelling were measured, the expression of voltage-dependent anion channel (VDAC)was assayed by immunohistochemistry in the heart, liver and kidney among the different groups after 8 weeks. Results (1)Compared with DM group, mitochondrial membrane potential in the heart,liver and kidney were significantly elevated in DM± MT group (553.6± 193.5 vs. 311.4 ± 133.7;745.7±115.8 vs. 358.9±158.7; 951.6±246.1 vs. 425.8±177.9, all P＜0.05). (2)Compared with DM group, mitochondrial swelling in the heart, liver and kidney was reinforced in DM ± MT group. (3)Compared with DM group, the expressions of VDAC in the heart, liver and kidney were significantly up-regulated in DM± MT group (76.93 ± 8.263 vs. 58.59 ± 7.62, 50.69 ± 6.33 vs.40.11±6.30, 77.86±8.59 vs. 61.44± 12.86, all P＜0.05). Conclusions Melatonin has protective effect on the activity of mitochondria in the heart, liver and kidney in diabetic rats possibly by up-regulating the expression of VDAC.

Objective To investigate the significance of test of receptor activator of nuclear factor?kappa B(NF?κB)ligand(RANKL)in serum and urine for the diagnosis of osteoporosis. Methods A total of 53 patients with osteoporosis(the experimental group)and 45 healthy controls(the normal control group)were recruited in this study. The expression levels of RANKL in serum and urine was measured and compared by enzyme?linked immunosorbent assay. Results The serum and urine levels of RANKL in the experimental group were significantly higher than those in the normal control group(P<0.01). The areas under receiver operating characteristic(ROC)curve of serum and urine RANKL were 0.898 and 0.734, respectively. The combined detection of serum and urine RANKL and Ca2+reached a high sensitivity of 89.5%and a specificity of 86.1%for diagno?sis of osteoporosis. Conclusion RANKL may be closely associated with the progression of osteoporosis. Serum and urine RANKL test may be help?ful in the diagnosis of osteoporosis.

OBJECTIVETo investigate the clinicopathological and prognostic significance of the c-kit protein in gastrointestinal stromal tumor (GIST).

METHODSParaffin embedded materials from 53 benign GISTs, 13 potentially malignant and 55 malignant cases were analysed for c-kit expression by immunohistochemical method, while using leiomyomas and schwannomas as controls. Positive signals were shown in cytoplasma and cell membrane.

RESULTSOf 122 GISTs, 118 (97%) were positive for c-kit. Localization of positive signals was accurate. The rate of c-kit protein in benign, potentially malignant and malignant cases was 98% (53/54), 93% (12/13), 96% (53/55) respectively. Compared with benign GIST, the positivity of c-kit in metastasis or recurrent cases decreased, but c-kit protein expression rate was not significantly different between the three patterns of GIST (chi(2) = 1.167, P > 0.05). Leiomyomas and schwannomas were typically c-kit negative.

CONCLUSIONAs a sensitive and specific marker of GIST, c-kit seems to be a useful antibody in the diagnosis and differential diagnosis of GIST, but it may not be used as a prognostic index.

Biomarkers, Tumor ; biosynthesis ; genetics ; Diagnosis, Differential ; Gastrointestinal Neoplasms ; diagnosis ; metabolism ; Humans ; Immunohistochemistry ; Mutation ; Prognosis ; Proto-Oncogene Proteins c-kit ; biosynthesis ; genetics

OBJECTIVE:To systematically evaluate therapeutic efficacy of modified Shenqi dihuang decoction in the treatment of chronic glomerular nephritis. METHODS:Retrieved from Wanfang database,CNKI,VIP,CBM,Cochrane Library,Medline, EMBase and PubMed,randomized controlled trials(RCTs)about modified Shenqi dihuang decoction combined with conventional therapy and (or) other Chinese patent medicine (trial group) vs. conventional therapy and (or) other Chinese patent medicine (control group)in the treatment of chronic glomerular nephritis were collected. Meta-analysis was carried out by using Rev Man 5.3 software after literature scanning,data extraction and quality evaluation. Stata 14.0 software was used to conduct Egger test to evaluate publication bias. If publication bias existed,the effect of publication bias on outcome was further evaluated by scissor compensation. TSA v0.9 software was used for trial sequential analysis(TSA)of total efficency. RESULTS:A total of 10 RCTs were included,involving 707 patients. The results of Meta-analysis showed that total response rate of trial group [RR＝1.40,95%CI(1.22, 1.61),P＜0.001] was significantly higher than that of control group; the level of urine protein [SMD＝－1.97,95%CI(－2.92,－1.03),P＜0.001] and Scr [MD＝－28.41,95%CI(－38.95,－17.87),P＜0.001] in trial group were significantly lower than control group,with statistical significance. Publication bias test of total response rate was conducted,and results of it showed that there was publication bias,but bias did not affect the results of this study. TSA analysis showed that the evidence of Meta-analysis was false positive. CONCLUSIONS:Therapeutic efficacy of modified Shenqi dihuang decoction for chronic glomerular nephritis need to be proved by more stringent RCTs.

The protective effect and mechanism of Oroxylin A, a naturally occurring compound in Scutellaria baicalensis Georgi, was investigated in this study. Isoproterenol administration to rats triggered classic cardiac failure, as demonstrated by objective parameters of cardiac dysfunction. Intragastric administration of oroxylin A at the dose of 25, 50 and 100 mg/(kg·d)significantly improved deranged cardiac parameters in the isoproterenol-induced heart failure model in a dose-dependent manner. At the same time, oroxylin A markedly ameliorated cardiac histological changes and down-regulated serum levels of various neuroendocrine factors including norepinephrine, aldosterone, brain natriuretic peptide, endothelin 1, angiotensin II and so on. Mechanistically, augmenting autophagy of myocardial cells via the inhibition of AKT1-RPS6KB1 signaling contributed to the improvement of isoproterenol-induced rat heart failure by oroxylin A. Taken together, these results suggest that oroxylin A ameliorates heart failure through promoting autophagy in myocardial cells.

Objective:To evaluate the efficacy of continuous infusion of lidocaine via urinary catheter for postoperative analgesia in patients undergoing urological surgery.Methods:Forty male American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients, aged 65-75 yr, with body mass index of 18-25 kg/m 2, scheduled for elective percutaneous nephrolithotomy, were divided into 2 groups ( n=20 each) using a random number table method: continuous infusion of lidocaine through urinary catheter group (group L) and patient controlled intravenous analgesia (PCIA) group (group PCIA). All the patients underwent total intravenous anesthesia, and a matched type of sterile urethral irrigation catheter was inserted after the operation.In group L, 0.5% lidocaine was continuously infused at a rate of 5 ml/h via the urinary catheter, while the equal volume of 0.9% normal saline was continuously infused via the urinary catheter, and PCIA was connected in group PCIA.PCIA solution contained sufentanil 125 μg (diluted to 250 ml in normal saline), and the PCA pump was set up with a 5 ml bolus dose, a 15 min lockout interval and background infusion at a rate of 5 ml/h.When visual analogue score was>4, sufentanil 0.05 μg/kg was injected intravenously as rescue analgesic.The development and severity of catheter-related bladder discomfort (CRBD) were recorded immediately at the end of the operation (T 1), and at 6 h (T 2), 24 h (T 3) and 48 h (T 4) after the operation, respectively.Riker sedation-agitation scale (SAS) score was recorded at T 1, 2, and QoR-9 scale was recorded at T 3, 4.The concentrations of serum cortisol (Cor), norepinephrine (NE), epinephrine (E) and blood glucose (Glu) were measured by enzyme linked immunosorbent assay.First off-bed time, exhaust time, length of hospital stay after surgery, and the requirement for rescue analgesia and adverse reactions (nausea and vomiting, respiratory depression, hypotension, skin itching) within 48 h after the operation were recorded. Results:Compared with group PCIA, the incidence of CRBD and the severity were significantly decreased at T 1-4, SAS score was decreased at T 1, 2, QoR-9 score was increased at T 3, 4, Cor, NE, E and Glu concentrations were decreased at T 1-4, the incidence of postoperative rescue analgesia was decreased, first off-bed time, exhaust time and length of hospital stay after surgery was shortened, and the incidence of postoperative nausea and vomiting, respiratory depression, hypotension, skin itching was decreased in group L ( P<0.05). Conclusion:Continuous infusion of lidocaine through the urinary catheter can provide good postoperative analgesia, reduce postoperative stress response and adverse reactions, and facilitate early postoperative recovery in patients undergoing urological surgery.

Purpose: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer owing to high heterogeneity, aggressive nature, and lack of treatment options, which has a substantial deleterious effect on patients' lives. HOXD antisense growth-associated long noncoding RNA (lncRNA) (HAGLR) plays tumor-promoting roles in many cancers. In this study, we aimed to explore the role of HAGLR in TNBC. Methods: Quantitative real-time polymerase chain reaction assays were used to examine the expression of RNAs. Functional experiments were conducted to test the biological behavior of TNBC cells. Moreover, MS2-RNA immunoprecipitation, luciferase reporter, and RNA pulldown assays were conducted to verify the binding relationship between HAGLR, microRNA-143-5p (miR-143-5p), and serine- and arginine-rich splicing factor 1 (SRSF1). Results: HAGLR was found to be highly expressed in TNBC tissues and cells, and inhibiting HAGLR suppressed cell proliferation, migration, and invasion and promoted cell apoptosis in TNBC. Meanwhile, miR-93-5p was shown to bind to HAGLR and SRSF1. In addition, SRSF1 plays an oncogenic role in TNBC. Importantly, HAGLR could activate the Wnt signaling pathway by sponging miR-93-5p to upregulate SRSF1; thus, accelerating TNBC progression. Conclusion HAGLR could promote the progression of TNBC through the miR-93-5p/SRSF1 axis to activate the Wnt signaling pathway.