BACKGROUND:In recent years,the incidence of hyperuricemia caused by purine metabolism disorders has been increasing,which can induce inflammatory responses and lead to renal injury. OBJECTIVE:To explore the role and mechanism of solute carrier family 2 member 12(SLC2A12)in hyperuricemia-related renal injury. METHODS:Renal tubular cells(HK2 cells)were divided into five groups:HK2 group,HK2+uric acid group,HK2+uric acid+NC group,HK2+uric acid+siSLC2A12 group,and HK2+uric acid+siSLC2A12+MK-2206 group.HK2 cells were treated with uric acid and transfected with siRNA SLC2A12,followed by MK-2206 treatment to inhibit AKT expression.Cell proliferation was detected by CCK-8 assay.Apoptosis was detected by TUNEL assay.qRT-PCR and western blot assay were used to detect fibrogenic factors as well as activation of the AKT/FOXO3a pathway.The concentrations of inflammatory cytokines were measured by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION:(1)Uric acid treatment inhibited cell proliferation and promoted cell apoptosis in the HK2+uric acid group compared with the HK2 group.The proliferative ability of cells in the HK2+uric acid+siSLC2A12 group was further decreased and apoptotic cells were further increased compared with the HK2 group.Compared with the HK2+uric acid+siSLC2A12 group,the HK2+uric acid+siSLC2A12+MK-2206 group showed an increase in cell proliferation and a decrease in apoptotic cells.(2)Compared with the HK2 group,the connective tissue growth factor(CTGF),α-smooth muscle actin(α-SMA)and transforming growth factor beta(TGF-β)expressions increased in the HK2+uric acid group;CTGF,α-SMA and TGF-β expression further increased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,the CTGF,α-SMA and TGF-β expressions decreased.(3)Compared with the HK2 group,the expression of p-AKT,FOXO3a,and p-FOXO3a elevated in the HK2+uric acid group;the expression of p-AKT further increased,while the expression of FOXO3a and p-FOXO3a decreased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,p-AKT expression decreased;FOXO3a and p-FOXO3a expression increased in the HK2+uric acid+siSLC2A12+MK-2206 group.(4)Compared with the HK2 group,interleukin-6,interleukin-1 β,and tumor necrosis factor α levels increased in the HK2+uric acid group;interleukin-6,interleukin-1 β,and tumor necrosis factor α levels further increased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,interleukin-6,interleukin-1 β,and tumor necrosis factor α levels diminished in the HK2+uric acid+siSLC2A12+MK-2206 group.(5)These findings indicate that SLC2A12 may protect against hyperuricemia-induced renal injury by counteracting uric acid-induced tubular fibrosis and inflammation through activation of the FOXO3a pathway.

BACKGROUND:Heterotopic ossification of skeletal muscle is a clinically serious complication.For heterotopic ossification of skeletal muscles,the cells involved in the process of heterotopic ossification remain unclear. OBJECTIVE:To investigate the involvement of myocytes,fascia cells,and endothelial cells in the process of heterotopic ossification in skeletal muscle and to observe the cell origin of heterotopic ossification in skeletal muscle induced by bone morphogenetic protein 4. METHODS:Both C2C12 cells and the myotubes formed by the C2C12 cells in the induction medium were cultured,and 500 ng/mL bone morphogenetic protein 4 was added to the medium respectively,and whether the C2C12 cells and myotubes continued to proliferate within 10 days under the treatment were observed under a microscope.Myogenic cells(L6,derived from rats)and fibroblast-derived cells(derived from human)were co-cultured.After treatment with 500 ng/mL bone morphogenetic protein 4 and 10 ng/mL transforming growth factor-β,osteogenic and chondrogenic differentiation potential within 21 days were observed using Safranine O staining and Alcian blue staining.Using transgenic animal FVB/N-TgN(TIE2-LacZ)182Sato mice,15 μL of adeno-associated virus-bone morphogenetic protein 4(5×1010 PFU/mL)were implanted in the thigh muscle space of genetic mice for 10 and 14 days.X-gal staining was used to observe the formation of new blood vessel endothelium in the differentiated bone. RESULTS AND CONCLUSION:(1)Bone morphogenetic protein 4 caused myotube breakdown and increased C2C12 cell proliferation.Compared with other groups,the pure fibroblast-derived cell group had a higher area of positive alcian blue and safarin O staining(P<0.05)and a lower area of alkaline phosphatase staining(P<0.05),while the pure L6 group had a bigger area of alkaline phosphatase staining(P<0.05)but a smaller area of positive alcian blue and safarin O staining(P<0.05).(2)Transplantation of adeno-associated virus-bone morphogenetic protein 4-adsorbed gelatin sponge into FVB/N-TgN(TIE2-LacZ)182Sato mice resulted in heterotopic ossification.(3)X-gal staining results demonstrated that there was no obvious staining in chondrocytes and differentiated bones and Tie2+ endothelial cells did not participate in the formation of the alienated bone.(4)These findings verify that fibroblasts are the primary source of osteoblasts during the adeno-associated virus-bone morphogenetic protein 4-induced ectopic endochondral ossification in skeletal muscle,but myogenic cells are the main source of osteoblasts.Tie2+ endothelial cells might not be the cell source for cartilage and bone.

Excessive gestational weight gain has already become a global clinical and public health problem that seriously affects maternal health. Excessive gestational weight gain not only increases the cesarean section rate and induces adverse pregnant outcomes, but also affects offspring development and health. This article reviews the effects of excessive weight gain during pregnancy on offspring health and its underlying mechanisms. Excessive gestational weight gain may increase the risk of obesity, cardiovascular diseases, infectious diseases of the respiratory tract, diabetes, polycystic ovary syndrome, mental or psychological illness among offspring, and the pathophysiological mechanisms include inflammatory response, intestinal flora dysbiosis and epigenetics theory. However, further studies are required to validate these hypotheses and to evaluate the effect of excessive weight gain at different gestational stages on offspring health, so as to provide insights into reasonable management of weight gain during pregnancy and improvements of offspring health.

Objective:This paper is to propose a calibration model based on sine function which enables more choices to determine the functional relationship between the absorbance and the concentration of the tested substance.Methods:This paper uses Taylor series expansion and Levenberg-Marquardt to obtain the optimal parameters for the Sine model and then summarizes the characters of the Sine model. On the basis of these characters, this paper compares and evaluates the experimental data processed by the Sine model from four aspects: correctness, precision, linearity and correlation.Results:The generated sine function calibration model achieved deviations within ±3% of the national standard substance, precision ( CV%) less than 2%, and a linear correlation coefficient greater than 0.990 within the measurement range of 32-710 mg/L. The correlation coefficients between the sine model and other well-performing linear calibration models for 104 clinical samples were all greater than 0.990. Conclusions:The performance evaluation of the prealbumin assay kit using the sine function calibration model meets industry standards and shows good correlation with the results of clinical sample measurements. This indicates that the sine function calibration model can serve as a new calibration model for in vitro diagnostic research and clinical applications.

Kidney transplantation is the most fundamental treatment for patients with end-stage renal disease. However, due to the long-term malnutrition of the patient before transplantation, coupled with the use of stress stimulation, immunosuppressive agents, and high-dose hormones after kidney transplantation, the patient is in a hypermetabolic state, and malnutrition is aggravated. The nutrition status of patients has a significant impact on the prognosis and development of kidney transplantation. Therefore, this article reviews the current status of nutrition intervention, the assessment of malnutrition, the related factors of malnutrition, and nutrition management in kidney transplantation recipients, so as to provide a reference for the nutrition and diet management of kidney transplantation recipients.

The rapidly developing resistance of cancers to chemotherapy agents and the severe cytotoxicity of such agents to normal cells are major stumbling blocks in current cancer treatments. Most current chemotherapy agents have significant cytotoxicity, which leads to devastating adverse effects and results in a substandard quality of life, including increased daily morbidity and premature mortality. The death receptor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can sidestep p53-dependent pathways to induce tumor cell apoptosis without damaging most normal cells. However, various cancer cells can develop resistance to TRAIL-induced apoptosis via different pathways. Therefore, it is critical to find an efficient TRAIL sensitizer to reverse the resistance of tumor cells to TRAIL, and to reinforce TRAIL's ability to induce tumor cell apoptosis. In recent years, traditional Chinese medicines and their active ingredients have shown great potential to trigger apoptotic cell death in TRAIL-resistant cancer cell lines. This review aims to collate information about Chinese medicines that can effectively reverse the resistance of tumor cells to TRAIL and enhance TRAIL's ability to induce apoptosis. We explore the therapeutic potential of TRAIL and provide new ideas for the development of TRAIL therapy and the generation of new anti-cancer drugs for human cancer treatment. This study involved an extensive review of studies obtained from literature searches of electronic databases such as Google Scholar and PubMed. "TRAIL sensitize" and "Chinese medicine" were the search keywords. We then isolated newly published studies on the mechanisms of TRAIL-induced apoptosis. The name of each plant was validated using certified databases such as The Plant List. This study indicates that TRAIL can be combined with different Chinese medicine components through intrinsic or extrinsic pathways to promote cancer cell apoptosis. It also demonstrates that the active ingredients of traditional Chinese medicines enhance the sensitivity of cancer cells to TRAIL-mediated apoptosis. This provides useful information regarding traditional Chinese medicine treatment, the development of TRAIL-based therapies, and the treatment of cancer.

Objective:To investigate the clinical treatment of large segmental humeral defects with unilateral external fixation and bone transport.Methods:A retrospective study was conducted of the 9 patients who had been treated at Department of Orthopedics, Shenzhen People's Hospital for large segmental humeral defects from September 2017 to June 2019. They were 5 males and 4 females with an average age of 29 years (from 21 to 41 years). Their defects were caused by trauma in 2 cases, by chronic osteomyelitis in 6 cases and by bone tumor in one case. The length of bone defect ranged from 4.2 to 9.0 cm, with an average of 5.9 cm. A unilateral external fixator was placed in operation, and adjusted regularly 7 to 10 days after operation for bone transport and bone lengthening to restore the length of humerus gradually. The external fixation bracket was removed after 3 to 4 layers of cortex were observed on X-ray films. Recorded were length and rate of humeral lengthening, fracture healing time, time for carrying external fixator and complications; the Disabilities of the Arm, Shoulder and Hand (DASH) scores were compared between preoperation and 15 months postoperation.Results:All the patients were followed up for 15 to 36 months (mean, 19 months). The length of lengthening averaged 5.9 cm (from 4.2 to 9.0 cm) with an average lengthening rate of 26%, the healing index 31 d/cm, the bone healing time 8.3 months, and the time for carrying external fixator 10.8 months(from 8.0 to 13.5 months). Their average DASH scores improved significantly from 25.0 ± 2.4 preoperation to 12.0 ± 1.8 at 15 months postoperation ( P<0.05). Good correction of large humeral defects was achieved in all but one case who reported temporary radial nerve paralysis. There were no such complications as neurovascular injury. The shoulder and elbow functions were basically normal after operation. Conclusions:In the treatment of large segmental humeral defects, unilateral external fixation plus bone transport can quickly repair the defects and recover the upper limb function of the patients.

Objective:To investigate the value of texture analysis based on T 2WI and apparent diffusion coefficient (ADC) maps in discriminating low grade from high grade prostate cancer (PCa). Methods:Retrospective analysis was performed on patients who were confirmed to be PCa by pathology after surgery and underwent MRI examination in the department of radiology,Tongji Hospital,Tongji Medical College, Huazhong University of Science and Technology before radical surgery, including routine T 1WI, T 2WI and diffusion weighted imaging (DWI) sequences. 3D data analysis module of the MaZda software was used to manually draw region of interest (ROIs) slice by slice on T 2WI and ADC images, and generate volume of interest (VOI) of the entire tumor. MaZda software was also used to extract texture features. The independent sample t test or Mann-Whitney U test were used to identify the texture features with statistically significant differences between low and high grade PCa groups. Lasso regression model was used to select the best combination of texture features for identifying low and high grade PCa, and then the model was built. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of the model in both training cohort and test cohort. Results:The best texture feature combination selected by Lasso regression model were the S (1, 0, 0) correlation of T 2WI and the S (1, 0, 0) correlation, S (1, -1, 0) sum entropy and vertical-run length nonuniformity of ADC maps. The area under the ROC curve (AUC) of the model in training cohort was 0.823, and the sensitivity and specificity were 70.4% and 80.8%, respectively, which were better than the single texture feature. The AUC of the model in test cohort was 0.714, which was worse than training cohort. Conclusion:The texture analysis of T 2WI and ADC maps is valuable for the identification of low and high grade PCa.

Pituitary adenoma is a common neuroendocrine tumor, and its complex pathogenesis makes its treatment a clinical problem. Recently, studies have shown that long non-coding RNA (LncRNA), as a class of endogenous RNA with a length of more than 200 nucleotides and basically no protein-coding function, plays an important regulatory role in various forms in multiple tumors including pituitary adenoma, and is closely related to the proliferation, invasion and metastasis of pituitary adenoma. Based on the latest research status at home and abroad, this paper summarizes the research progress of LncRNA in pituitary adenoma, hoping to provide new ideas for the diagnosis, treatment and prognosis of pituitary adenoma.

Chronic subdural hematoma (cSDH) occurs in acute subdural hemorrhage after head trauma or converts from effusion. Traditional treatment is based on conservative treatment and surgical drainage. The effective rate of conservative treatment is only 3%-18%; even with drilling drainage treatment, the recurrence rate is as high as 33%. Recently, the middle meningeal artery embolization technique based on pathological analysis can greatly reduce the recurrence rate, and the operation is simple and curative effect is exact. This article reviews the pathogenesis of cSDH and progress of interventional therapy.