Objective To construct nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)knockout mice in order to investigate the effects of NLRP3 knockout on radiation-induced acute pneumonitis and pulmonary fibrosis.Methods Nlrp3+/+and Nlrp3-/-mice were randomly divided into the control group and irradiation group.To induce radiation-caused acute pneumonitis,the control group was exposed to sham irradiation while the irradiation group was exposed to 60Co γ-rays at a dose of 22 Gy at a dose rate of 184.30 R/min.At 14 days post-irradiation,the body weight of each mouse and the wet weight of its lung tissue were measured separately using an analytical balance to calculate the lung coefficient.Quantitative real-time PCR(qPCR)and cytometric bead array(CBA)were used to detect inflammatory responses in lung tissues and serum.Hematoxylin-eosin(HE)staining and F4/80 immunohistochemical staining were used to assess pathological changes and inflammatory cell infiltration in lung tissues.Cysteinyl aspartate specific proteinase-1(caspase-1)activation was analyzed by Western blotting.To establish a model of radiation-induced pulmonary fibrosis,mice were irradiated with 60Co γ-rays at a dose of 18 Gy at a dose rate of 174.67 R/min.At 24 weeks post-irradiation,HE staining and Masson staining were performed to evaluate pulmonary fibrosis.Results NLRP3 knockout inhibited caspase-1 activation,reduced inflammatory responses in lung tissues and serum,suppressed macrophage infiltration,alleviated pulmonary edema,and thereby protected against acute radiation-induced lung injury.Additionally,NLRP3 knockout significantly ameliorated late-stage radiation-induced pulmonary fibrosis.Conclusion NLRP3 knockout can mitigate both early radiation-induced pneumonia and lateradiation-induced pulmonary fibrosis.

Renal fibrosis is a common and irreversible pathological feature of end-stage renal disease caused by multiple etiologies. The role of inflammation in renal fibrosis tissue has been generally accepted. The latest view is that fatty acid metabolism disorder contributes to renal fibrosis. peroxisome proliferator activated receptor-gamma coactivator 1α (PGC1α) plays a key role in fatty acid metabolism, regulating fatty acid uptake and oxidized protein synthesis, preventing the accumulation of lipid in the cytoplasm, and maintaining a dynamic balanced state of intracellular lipid. In multiple animal models of renal fibrosis caused by acute or chronic kidney disease, or even age-related kidney disease, almost all of the kidney specimens show the down-regulation of PGC1α. Upregulation of PGC1α can reduce the degree of renal fibrosis in animal models, and PGC1α knockout animals exhibit severe renal fibrosis. Studies have demonstrated that AMP-activated protein kinase (AMPK), MAPK, Notch, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), epidermal growth factor receptor (EGFR), non-coding RNA (ncRNAs), liver kinase B1 (LKB1), hairy and enhancer of split 1 (Hes1), and other pathways regulate the expression of PGC1α and affect fatty acid metabolism. But some of these pathways interact with each other, and the effect of the integrated pathway on renal fibrosis is not clear.
Animals ; Fatty Acids ; Fibrosis ; Lipid Metabolism ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism* ; Renal Insufficiency, Chronic

OBJECTIVES: To investigate the role of autophagy in oxalate-induced toxicity of human proximal renal tubular epithelial cell (HK-2). METHODS: HK-2 cells were exposed to oxalate (1 mmol/L) for 2 h and 3-methyladenine (3-MA) was used to inhibit autophagy. Then Western blotting was used to measure the expression of autophagy-related protein LC3II. Cell viability and cell apoptosis were measured by MTT assay and flow cytometry assay, respectively. RESULTS: Cytoplasmic vacuolization was observed in HK-2 cells after treating with oxalate for 2 h. However, 3-MA showed no effects on the formation of cytoplasmic vacuolization regardless of the dose at 1 or 5 mmol/L. The expression of LC3II protein was significantly increased in the HK-2 cells in the presence of oxalate (0.62±0.03 vs 0.35±0.02, CONCLUSIONS Autophagy of HK-2 cells is enhanced by oxalate at the concentration of 1 mmol/L. Inhibition of 3-MA-induced autophagy protects HK-2 cells from the oxalate-induced cytotoxicity.
Apoptosis ; Autophagy ; Cell Line ; Epithelial Cells ; Humans ; Oxalates/toxicity*

Squamous cell carcinoma (SCC) of the renal pelvis is extremely rare and hardly to be diagnosed due to its lack of specificity in clinical manifestations and traditional imaging features. We reported a case with history of multiple operations for double kidney stones, who was admitted to our hospital twice due to "right kidney ureteral stones, left kidney complex stones, chronic renal insufficiency and urinary tract infection" . During this period, a total of 6 surgeries were performed. In the first 19-day hospitalization, right transurethral ureteroscopic lithotripsy and right percutaneous nephroscope lithotripsy(PCNL)were performed respectively. And 20 days later, the patient was admitted to hospital again for management of left complex kidney stones, and the left side PCNL was performed for 4 times within 27 days. During the two hospitalizations, no tumor was reported during the three times of contrast-enhanced CT examination of the urinary system. The patient continued to have fever after the 4th time of left PCNL, with failure of anti-infection treatment. Then, the of the left renal pelvis was considered clinically, and left nephrectomy was suggested after communication with the patient and his family members. Postoperative pathology confirmed renal pelvis SCC. After surgery, the patient’s temperature was back to normal and then discharged. The patient died 3 months after discharging due to the systemic metastasis.

OBJECTIVE: To report on the clinical pictures of 7 patients from a pedigree affected with X-linked adrenal hypoplasia congenita (XL-AHC) and hypogonadotropic hypogonadism (HH) and the underlying mutations. METHODS: Seven patients were identified from a four-generation pedigree affected with XL-AHC and HH. Their clinical features, endocrinological changes, treatment and drug response were recorded. The patients were subjected to next-generation sequencing, and the result was verified by Sanger sequencing. PolyPhen-2 was used for predicting the influence of the mutation on protein production. RESULTS: Three deceased patients had manifested adrenal insufficiency (AI) within one year after birth. Two died at 6 and one died at 12. The four survivors presented with salient clinical and endocrinological features of AHC and HH, adrenal and testicular atrophy, and renin-angiotensin compensation. Two adult patients had testicular micro-stone detected by ultrasound.One of them also had remarkable seminiferous tubule degeneration by biopsy. The patients were followed up for 0.5 to 10 years. All required hyper-physiological dose of hydrocortisone to stabilize their clinical condition. In three patients, gonadotropic or androgen replacement induced cardinal masculine development but with unsatisfactory testis growth and sperm production.Genetic analysis revealed a novel missense c.827A>C (p.Q276P) mutation in a hotspot region within a highly conserved domain. PolyPhen-2 predicted the mutation to be highly hazardous. CONCLUSION The novel p.Q276P mutation of the DAX1 gene probably underlies the XL-AHC and HH in this pedigree with variable clinical presentations in the patients.
Adrenal Insufficiency ; DAX-1 Orphan Nuclear Receptor ; genetics ; Humans ; Hypoadrenocorticism, Familial ; genetics ; Male ; Mutation ; Mutation, Missense ; Pedigree ; Repressor Proteins

Objective: To observe the cellular damage of low-dose combined exposure to Hg, Pb and Cd on hippocampal neurons in rat. Methods: SH-SY5Y cells were randomly divided into 8 groups by 2×2×2 factorial design: control group, Pb exposure group, Hg exposure group, Pb+Hg exposure group, Pb+Cd exposure group, Hg+Cd exposure group and Pb+Cd+Hg exposure group. And the cell viabilities were measured. On this basis, an animal model was established. Twenty eight-week-old SD pregnant rats were randomly divided into four groups by random number table, and five in each group: the control group(distilled water), 1-fold metal mixture exposure group (1×MM, poisoning solution containing mercury chloride 0.15 mg/L, lead acetate trihydrate 25 mg/L, cadmium chloride 7.5 mg/L), 5-fold metal mixture exposure group (5×MM, poisoning solution containing mercury chloride 0.75 mg/L, lead acetate trihydrate 125.00 mg/L, cadmium chloride 37.50 mg/L), 10-fold metal mixture exposure group (10×MM, poisoning solution containing mercury chloride 1.50 mg/L, lead acetate trihydrate 250.00 mg/L, cadmium chloride 75.00 mg/L). Pregnant rats drank water until delivery. Twenty male pups were selected and exposed to these metals through breast milk until weaned. The heavy metals dose of poisoning water was adjusted, and then the weaned rats were exposed to heavy metals via drinking poisoning water until adulthood (postnatal day 83). The blood samples and brain hippocampus samples were collected to observe the ultrastructural changes of hippocampus, and to determine the levels of Hg, Pb and Cd in blood. In addition, apoptosis rate and fluorescence intensity of reactive oxygen species and intracellular free calcium concentration ([Ca²⁺]_i) in hippocampal neurons were measured. Results: Cellular factorial design analysis showed that Hg+Pb+Cd (at no observed adverse effect level, 1.0, 0.5 and 0.1 μmol/L, respectively)had a interaction on cell viability after 48 or 72 hours of combined exposure (P<0.05). The results of ultrastructure showed that mitochondria decreased, ridges and matrixes gradually dissolved in rat hippocampal neurons of 5×MM group; nuclear chromatin aggregated, more ridges and matrixes dissolved and the mitochondria also decreased in rat hippocampal neurons of 10×MM group. The concentration of Hg, Pb and Cd in the blood of 1×MM group, 5×MM group and 10×MM group were higher than those in the control group, and the differences were statistically significant (P<0.001). There was no significant difference in apoptosis rate between the 1×MM group and the control group. The apoptosis rate of 5×MM group and 10×MM group was higher than that in the control group, and the differences were statistically significant (P<0.001). There was no statistically significant difference in the fluorescence intensity of reactive oxygen species in hippocampal neurons of the 1×MM group and the control group. The fluorescence intensity of reactive oxygen species in the 5×MM group and the 10×MM group was higher than that in the control group, the difference was statistically significant (P<0.05). There was no significant difference in the fluorescence intensity of [Ca²⁺]_i between the 1×MM group and the control group. The fluorescence intensity values of [Ca²⁺]_i in the 5×MM group and the 10×MM group were higher than the control group, the differences were statistically significant (P<0.001). Conclusion Low-level combined exposure to Hg, Pb, and Cd caused synergistic neurotoxic damage, and the process may be related to the changes of neuronal apoptosis, reactive oxide species, and [Ca²⁺]_i levels.

Objective To investigate the efficacy of preemptive analgesiawith ultrasound-guided modified dorsal penile nerve block combined ketorolac tromethamine for circumcision in pediatric patients.Methods Forty-five pediatric patients with ASA grade Ⅰ undergoing elective circumcision were randomly divided into 3 groups (n=15 each).The same intravenous compound anesthesia was used in the three groups.The pediatric patients underwent ultrasound-guided modified dorsal penile nerve block with a mixture of 0.1 ml/kg of 0.2% ropivacaine and 0.8% lidocaine before operation in group A and group B.The pediatric patients were given ketorolac tromethamine 1 mg/kg intramuscular injection before operation in group A and group C.The total consumption of propfol and sufentanil, occurrence of intraoperative body movement and respiratory depression, emergence time, time from waking up to going out of PACU and adverse reactions such as postoperative agitation, nausea, vomiting and pruritus were aslo recorded.The requirement for postoperative paracetamol suppositories was recorded.Results Compared with group C, the total consumption of propfol and sufentanil were significantly decreased, incidence of body movement andrespiratory depression were significantly decreased, the emergence time and time from waking up to going out of PACU was significantly shortened, requirement for paracetamol suppositories were significantly decreased in group A and group B(P<0.05).Compared with group B, incidence of requirement for paracetamol suppositories was significantly decreased in group A (P<0.05).No pediatric patients developed postoperative nausea, vomiting, pruritus and incidence of emergence agitation had no statistical difference in the three groups.Conclusion Preemptive analgesia with ultrasound-guided modified dorsal penile nerve block combined ketorolac tromethamine is safe and effective when used for circumcision in pediatric patients, and it has good efficacy of postoperative analgesia.

Objective:To investigate the sleep quality and relative factors of the people aged 18years or over in Tianjin Municipality.Methods:The participants came from the Tianjin Mental Health Survey conducted from Ju-ly to December in 2011.Total of 11618 residents aged 18 years or over were selected randomly among the general population and finished the Pittsburgh Sleep Quality Index (PSQI)for assessment of sleep quality and General Health Questionnaire (GHQ-12)for screening out the individual with possible mental disorders.The PSQI total score >7 was defined as poor sleep quality.Chi-square test and Wilcoxon rank sum test was used to conduct univa-riable analysis,and logistic regression was used to analyze the related factors to poorer sleep quality.Results:In this sample,980 people had poorer sleep quality,with the adjusted prevalence rate in Tianjin was 6.6%.Logistic regres-sion analysis showed risk factors to poorer sleep quality were female (OR =1.47,95%CI:1.19 -1.82),older age (30 -39 years old,40 -49 years old,50 -59 years old,60 -69 years old,70 years or older,OR =1.72(95%CI:1.10 -2.69),2.55(95%CI:1.66 -3.91),4.41 (95%CI:2.85 -6.83),5.34(95%CI:3.32 -8.59),5.40(95%CI:3.21 -9.08),at his/her own expense on medicare (OR =1.52,95%CI:1.15 -2.00),unemployment (OR =1.46,95%CI:1.05 -2.03)or retirement (OR =1.45,95%CI:1.02 -2.06),smoking (OR =1.49,95%CI:1.22-1.83),difficulty to engage in daily work or activities due to physical illness (OR =2.30,95%CI:1.85 -2.85), and GHQ -12 score ≥ 4 (OR =6.51,95%CI:5.46 -7.46).Conclusion:Although the prevalence rate of poorer sleep quality in the people aged 18 years or over in Tianjin is lower,the problem is common and should not to be ignored.

Objective To evaluate the effect of α-lipoic acid on the cognitive function after cardiopulmonary bypass (CPB) in diabetic rats.Methods Health adult male Sprague-Dawley rats,weighing 400-500 g,aged 16-22 weeks,were used in this study.Diabetes mellitus was induced by intraperitoneal streptozocin 60 mg/kg and confirmed by blood glucose≥ 16.7 mmol/L.Thirty-two diabetic rats were randomly divided into 2 groups (n =16 each):diabetes mellitus group (group D) and α-lipoi cacid group (group L).In group L,α-lipoic acid 30 mg/kg was intraperitoneally injected once a day for 7 consecutive days starting from 6th week after induction of diabetes mellitus.While the equal volume of normal saline was given instead in group D.The two groups underwent CPB after the last administration.Before induction of diabetes mellitus,on 5th week after induction of diabetes mellitus,before CPB,at the end of CPB,and on 3 and 5 days after termination of CPB,10 rats were chosen from each group and venous blood samples were collected for determination of plasma TNF-α and IL-10 concentrations.Ten rats in each group were chosen for detection of cognitive function before induction of diabetes mellitus,before CPB and 5 days after termination of CPB.The rats were then sacrificed and hippocampi were isolated for measurement of NF-κB activity.Results Compare with group D,the plasma TNF-α concentration,times of electric shock and activity of NF-κB in hippocampal tissues were significantly decreased and the plasma IL-10 concentration was increased in group L (P ＜ 0.05 or 0.01).Conclusion α-lipoic acid can improve the cognitive function after CPB in diabetic rats and inhibition of activation of NF-κB in hippocampal neurons is involved in the mechanism.