Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.
Animals ; Mice ; Candida albicans ; Candidiasis, Oral/drug therapy* ; Antifungal Agents/pharmacology* ; Hyphae ; Artemisinins/pharmacology*

Objective:To compare the effect of percutaneous screw-rod system combined with sacroiliac screw internal fixation and non-operation of type II-IV fragility fracture of the pelvis (FFP).Methods:A retrospective multicentral cohort study was performed to analyze the clinical data of 74 patients with FFP treated in Jiangjin Central Hospital of Chongqing and Hechuan People′s Hospital of Chongqing from January 2017 to June 2021, including 23 males and 51 females, aged 62-95 years [(79.3±7.3)years]. A total of 41 patients received non-surgical treatment (non-operation group). and 33 patients received percutaneous screw-rod system combined with sacroiliac screw internal fixation (operation group). The time to get out of bed, visual analog scale (VAS) and Majeed score on admission and at 1, 3, 6, 12 months after treatment, fracture healing time and complications were evaluated in the two groups.Results:Except for 9 patients who died at 3-9 months after treatment, the remaining patients were followed up for 12-24 months [(13.5±3.2)months]. The time to get out of bed was (11.4±2.8)days in operation group and was (67.4±4.4)days in non-operation group ( P<0.01). The VAS and Majeed score at 1, 3, 6 and 12 months after treatment were significantly improved in both groups compared with those on admission (all P<0.05). There was no significant difference in VAS and Majeed score between the two groups on admission (all P>0.05). The VAS was (3.2±0.7)points in operation group compared to (4.2±0.8)points in non-operation group at 1 month after treatment, and was (1.8±0.5)points in operation group compared to (2.9±0.7)points in non-operation group at 3 months after treatment (all P<0.01). The Majeed score was (56.0±2.4)points in operation group compared to (40.4±2.7)points in non-operation group at 1 month after treatment; the score was (77.3±2.6)points in operation group compared to (57.7±4.2)points in non-operation group at 3 months after treatment; the score was (86.5±1.8)points in operation group compared to (79.6±2.8)points in non-operation group at 6 months after treatment (all P<0.01). In contrast, the two groups had no statistically significant difference in VAS at 6 months and 12 months after treatment and Majeed score at 12 months after treatment (all P>0.05). There was no statistically significant difference in the fracture healing time between the two groups ( P>0.05). There was no statistically significant difference in the incidence of complications related to fixation methods between the two groups ( P>0.05). The incidence of bed-related complications was 24.2% (8/33) in operation group and was 51.2% (21/41) in non-operation group ( P<0.05). The 1-year fatality rate was 3.0% (1/33) in operation group and 19.5% (8/41) in non-operation group ( P<0.05). Conclusion:Compared with non-operative treatment, percutaneous screw-rod system combined with sacroiliac screw internal fixation in the treatment of type II-IV FFP can allow early off-bed movement, effectively relieve pain, improve quality of life of the patients, and reduce complication rate.

Objective:To compare the difference between breast bracket combined with polyurethane foam and single polyurethane foam in the accuracy of immobilization, providing a better immobilization for breast cancer radiotherapy.Methods:Fifty breast cancer patients who received radiotherapy in Sun Yat-sen University Cancer Center from March 2021 to July 2021 were selected. Among them, 25 patients were immobilized with polyurethane foam (foam group), and the other 25 patients were immobilized with polyurethane foam combined with breast bracket (combination group). All patients were scanned by CBCT once a week to obtain setup errors in the SI, LR and AP directions for t-test. The formula M PTV=2.5 Σ+0.7 σ was used to calculate the margin of the planning target volume(M PTV). Results:The setup errors in the foam group were SI (2.0±3.26) mm, LR (0.88±2.76) mm, AP (1.22±3.55) mm, Rtn -0.24°±0.85°, Pitch 0.16°±1.11°, Roll -0.32°±1.05°, and the M PTV were 6.75 mm, 8.46 mm and 8.73 mm, respectively. The setup errors in the combination group were SI (1.0±3.01) mm, LR (0.62±2.74) mm, AP (1.82±3.21) mm, Rtn 0.64°±0.59°, Pitch 0.71°±1.22°, Roll 0.29°±0.73°, and the M PTV were 6.35 mm, 7.47 mm, and 7.61 mm, respectively. After comparing the setup errors in the three-dimensional directions between two groups, the t value of LR, SI, AP and Rtn, Pitch, Roll was -4.304, -2.681, 1.384, and -9.457, -3.683, -5.323, respectively. And the differences in the LR, SI, Rtn, Pitch and Roll directions were statistically significant (all P<0.05). Conclusions:The immobilization effect of polyurethane foam combined with breast bracket is better and the M PTV is also smaller than those of polyurethane foam alone. Therefore, it is recommended to use polyurethane foam combined with breast bracket for immobilization in breast cancer radiotherapy.

Objective:To investigate the clinical feasibility of the Unity radiotherapy system guided by magnetic resonance imaging.Methods:Twenty-four patients were enrolled and received a total of 384 fractions of treatment at Unity system. According to the treatment site, all patients were divided into head-neck, abdomen-thorax, pelvic, spine and limb groups. The patients were set-up without external laser. And then, the time required at different stages in online treatment process and the registration error of each fraction were separately calculated. The geometric deformations of MR images were weekly measured by using MR geometric deformation phantom. At last, the Arccheck was used to perform the dose verification of reference plan, online plan and offline plan.Results:The mean duration of radiotherapy in the five groups were 29.1, 27.6, 26.6, 25.6 and 32.0 min, respectively. The set-up errors in the left-right, superior-inferior and anterior-posterior direction in the five groups were: head-neck group (0.08±0.06 cm, 0.16±0.13 cm, 0.08±0.05 cm), abdomen-thorax group (0.23±0.18 cm, 0.50±0.47 cm, 0.12±0.1 cm), pelvic group (0.25±0.19 cm, 0.32±0.25 cm, 0.11±0.09 cm), spine group (0.46±0.38 cm, 0.26±0.26 cm, 0.13±0.07 cm) and limb group (0.33±0.30 cm, 0.34±0.23 cm, 0.08±0.06 cm), respectively. In the central region, the geometric deformation of MR was less than 0.3 mm, and that of the sphere with a diameter of 500 mm was less than 2.1 mm. The meanγ pass rate of the reference plan, online plan and offline plan were 97.92%, 97.84% and 94.58%, respectively.Conclusions:MR-guided radiotherapy has great potential for clinical application, whereas the process of Unity system is relatively complex. The synergy of different departments has a great impact on the treatment, which needs further optimization.

Objective:To summarize the diagnosis and treatment process of abdominal involvement in 229 children with IgA vasculitis and to provide reference for clinic treatment.Methods:A total of 229 pediatric patients, diagnosed as IgA vasculitis with abdominal involvement admitted to the Department of Pediatric Nephrology of Shengjing Hospital, China Medical University from January 1st 2018 to December 31st 2019, were retrospectively analyzed in the study and were divided into three groups according to Numerical Rating Scale to compare indexes in different degrees of abdominal pain.Results:The duration of hospitalization was related with degree of abdominal pain, as the more severe the abdominal pain was, the longer the hospitalization time was( P<0.001). The incidence of bloody stool were also proportionate to the degree of abdominal pain( P<0.001). With the aggravation of abdominal pain, the proportion of intestinal wall edema increased, as the highest proportion was severe group( P<0.001). The proportion of renal involvement in severe group was significantly higher than that in non-severe group( P<0.001). Twenty cases of intestinal wall edema with decreasing of albumin were treated by intravenous hormone therapy after albumin infusion as the results of no intestinal complications occurred.Compared with the mild and moderate groups, the white blood cells of the severe group were higher( P<0.001)and the albumin was lower( P<0.05). It was no significant difference in hemoglobin, serum amylase and serum lipase among three groups.The mean value of CRP had no difference among three groups and was higher than that of normal.Interleukin(IL)-6 in severe group was higher than that in other two groups( P<0.05), but there was no significant difference in IL-2, IL-4, IL-10, IL-17 and tumor necrosis factor.In terms of treatment, 40 cases were treated with immunoglobulin and four cases with hemoperfusion.The average duration of intravenous glucocorticoid application was related to the degree of abdominal pain among three groups.The longest duration was severe group(16.00±6.91)d and the shortest one was mild group(6.71±3.75)d. Conclusion:Pediatric patients diagnosed as IgA vasculitis with severe abdominal pain whose part of inflammatory indexes increased and albumin decreased obviously should complete imaging examinations to evaluate the extent of intestinal wall edema.If diagnosed as hypoalbuminemia and intestinal wall edema distinctly, hormone therapy should be given after albumin infusion to prevent severe complications such as intestinal perforation.For pediatric patients of IgA vasculitis with severe abdominal symptoms, on the basis of hormone therapy, immunoglobulin and hemoperfusion could be used to quickly remove abnormal immune substances to slow down the disease.

Objective:To analyze the accuracy of diagnostic indicators for perioperative venous thromboembolism（VTE）in orthopedic patients.Methods:A retrospective case-control study was conducted to analyze the clinical data of 109 patients who underwent initial total hip arthroplasty（THA），total knee arthroplasty（TKA）or proximal femoral nail antirotation（PFNA）in Hechuan District People ’s Hospital of Chongqing from January 2015 to September 2019. There were 55 males and 54 females，with age range of 18-76 years［（46.3 ± 11.2）years］. Of all，54 patients underwent unilateral THA due to femoral head necrosis and femoral neck fracture，36 patients underwent unilateral TKA due to osteoarthritis and 19 patients underwent PFNA due to proximal femoral fracture. VTE was confirmed in 47 patients（VTE group），and did not occur in 62 patients（non-VTE group）. Venous blood was collected from all patients on admission and at postoperative 1，3，5，7 days to measure levels of plasma D-dimer，serum interleukin（IL）-18 and vascular endothelial growth factor（VEGF）. The accuracy of the above indicators in VTE diagnosis was analyzed by using receiver operating characteristic（ROC）curve. Results:In both groups，preoperative levels of D-dimer，IL-18 and VEGF were significantly lower than those postoperatively，and each indicator showed significant difference at each time points after operation（ P < 0.05 or 0.01）. Moreover，levels of D-dimer，IL-18 and VEGF in VTE group were significantly higher than those in non-VTE group at each time after operation（ P < 0.05 or 0.01）. Area under the ROC curve（AUC）for D-dimer was 0.839（95% CI 0.729-0.887），with the optimal cut-off of 5.5 μg/ml，sensitivity of 87.0%，specificity of 79.0% and Youden index of 0.67. AUC for IL-18 was 0.817（95% CI 0.719-0.857），with the optimal cut-off of 293.5 pg/ml，sensitivity of 67.0%，specificity of 87.1% and Youden index of 0.457. AUC for VEGF was 0.837（95% CI 0.784-0.918），with the optimal cut-off of 510.8 pg/ml，sensitivity of 81.0%，specificity of 79.0% and Youden index of 0.583. AUC for combined D-dimer，IL-18 and VEGF was 0.870（95% CI 0.747-0.992），with the sensitivity of 87.2%，specificity of 83.4% and Youden index of 0.606. Conclusions:For diagnosis of perioperative VTE in orthopedic patients，serum VEGF is relatively accurate，while serum IL-18 has a low accuracy. However，the diagnostic rate of VTE can be improved by combining indicators of D-dimer，IL-18 and VEGF.

Nephrotic syndrome is a common glomerular disease in childhood and easy to recur.It has been found that children with nephrotic syndrome are often accompanied by atopic manifestations and there is high co-morbidity between nephrotic syndrome and atopic diseases.This article reviewed the pathogenesis, cytokines and treatment of nephrotic syndrome and atopic diseases in children to explore the similarity between them to provide new clues and methods for the treatment of nephrotic syndrome in children.

Objective To investigate the dynamic changes of neutrophil gelatinase-associated lipoca-lin(NGAL) and kidney injury molecule 1(KIM-1) in children after contrast media administration and evalu-ate the effect of hydration therapy. Methods A total of 58 patients with urinary system diseases who were admitted to Shengjing Hospital of China Medical University from March 2012 to March 2014 for intravenous pyelography(IVP) in pediatric department were enrolled. The 58 patients were randomly divided into hydra-tion group of 28 patients and non-hydration group of 30 patients. Contemporaneous 24 patients received respiratory system enhanced CT examination without urinary tract diseases and hydration were enrolled as control group. Urine NGAL and KIM-1 of the three groups at 0 h,24 h,48 h,72 h,96 h after using intravenous contrast media were detected by ELISA. Serum creatinine of the three groups at 0 h,48 h,96 h after using intravenous contrast media were detected. Results All of the 82 subjects in this study didn′t occur contrast- induced acute kidney injury. The urinary NGAL of non-hydrated group significantly increased at 24 h and 48 h after contrast media administration ( P < 0. 05 ) and the urinary NGAL of hydrated group significantly increased at 48 h and 72 h(P<0. 05). But the urinary NGAL at 24 h and 48 h of the hydration group were lower than these of the non-hydrated group,there were statistically significant differences(P<0. 05). At 24 h,48 h and 72 h after contrast media administration,the level of urine KIM-1 in the non-hydration group sig-nificantly increased(P<0. 05). Urine KIM-1 at 48 h and 72 h in the hydration group significantly increased (P<0. 05). But the urine KIM-1 at 24 h,48 h and 72 h of the hydration group were lower than these of the non-hydration group,the differences were statistically significant(P<0. 05). Comparison of urine NGAL and KIM-1 at different times before and after contrast media administration in children receiving enhanced CT examination who without urinary tract disease showed no statistically significant differences ( P >0. 05 ). Conclusion The urine NGAL and KIM-1 of children with urinary system diseases increase after contrast media administration and there is a trend of spontaneous recovery. Hydration intervention can alleviate the up-ward trend of urine NGAL and KIM-1. For children receiving enhanced CT examination but without urinary system diseases,the change of urine NGAL and KIM-1 are not significant.

Objective To examine the clinical features and long - term outcome of pediatric IgA nephropathy and to explore the clinical effect of Mycophenolate Mofetil(MMF)and Cyclophosphomide(CTX)in children with IgA nephropathy with nephrotic syndrome(NS). Methods A single - centre,retrospective,observational study of 115 chil-dren with IgA nephropathy from 2004 to 2013 in Pediatric Nephrology of Shengjing Hospital of China Medical University was conducted. Demographic and clinical data were reviewed retrospectively for age,sex,medical history,presenting symptoms,medications,follow - up duration and the responsiveness to treatment. Results In all children,NS occurred in 20(17. 4% ). There were 35 patients(30. 4% )with non - NS and 60 patients(52. 2% )with isolated hematuria. No special treatment in patients with IgA nephropathy with isolated hematuria. Among patients with proteinuria less than 20 mg/(kg·d),12 patients were treated with angiotensin - converting - enzyme - inhibitor(ACEI),8 patients were trea-ted with ACEI and corticosteroid. At all time points,mean proteinuria was significantly decreased in ACEI and cortico-steroid group compared with ACEI group(P ﹤ 0. 001). Patients with 20 - 49 mg/(kg·d)proteinuria were treated with ACEI and corticosteroid. At all time points,mean proteinuria was significantly decreased compared with the prior time point. Patients with NS were treated with MMF and corticosteroid or CTX and corticosteroid. Eleven patients were trea-ted with MMF,9 patients were treated with CTX. A significantly difference was seen after 3 months in proteinuria greater decrease from pretreatment in CTX group than those in MMF group(P ﹤ 0. 001). No significant difference in proteinuria was observed at other time point. No significant change in white blood cell count was observed in MMF group and CTX group. No serious complication developed in any patient during treatment. During the median follow - up of 35. 2 months (range 4. 0 - 124. 6 months),no patient progressed to end stage renal disease. Conclusions IgA nephropathy patients with isolated hematuria should be long - term followed up. Children with non - nephrotic - range proteinuria should be treated with ACEI or corticosteroid. Patients with NS should be treated with corticosteroid and MMF or CTX. The long -term prognosis within 3 - 5 years should be good if proteinuria within normal range in pediatric IgA nephropathy pa-tients.

Paired box2 ( PAX2 ) is a transciption factor which mainly expressed in the developing kid-ney. Researches indicate that PAX2 promote the transcription through interactions with the adaptor PAX transac-tivation domain interacting protein(PTIP). Otherwise,PAX2 protein can lead to chromatin compaction and gene silencing through interactions with Grg4. PAX2 reexpressed in acute kidney injury and involved in promoting cell proliferation. Congenital PAX2 gene mutation is closely related to congenital abnormalies of the kidney and uri-nary tract. In chronic kidney disease,PAX2 promote proliferation and cyst formation. Here,the recent researches on the function of PAX2 and its role in acute kidney injury and chronic kidney disease are reviewed.