BACKGROUND: It was reported that the reason why the fracture healing become more and more difficult with the increasing age may be associated with the varied gene regulation of bone marrow mesenchymal stem cells differentiation into osteoblast and lipoblast. However, the exact mechanism under it remains poorly understood.OBJECTIVE: To explore the association of the age-related changes on expression of peroxisome proliferator-activated receptor γ (PPARγ) and core binding α1 (Cbfα1) with the age-relatad fracture healing impairment, we studied the expression changes of PPARγ and Cbfα1 during aging fracture healing.DESIGN, TIME AND SETTING: A randomized control animal trial was performed in the Third Xiangya Hospital of Central South University between October 2007 and Febuary 2008. MATERIALS: Six male SD rats of 3 months and the other six of 23 months, randomly-selected, were divided into two groups: the old experiment group (23 months) and the young control group (3 months). METHODS: Transverse osteotomies on the middle-upper parts of left tibiae were performed to the rats, with the self-made extemal mini-fixator implanted there simultaneously. Tractions were taken twice a day (0.2 mm/d) for 14 days from day 2 till day 15 post operation. On day 15 post operation, rats were sacrificed to harvest left tibea samples. MAIN OUTCOME MEASURES: Both imaging examination and histological observation were performed to the fractures of rats. The PPARγ and Cbfα1 expression were detected with reverse transcription-polymerase chain reaction (RT-PCR) technique. RESULTS: All samples were involved in the results analyses. The imaging examination showed that many osteotylus generated between the broken ends of fractures in the young control group; that the bone formation of the young control group was much better than that of the old experiment group. The histological observation showed that large amounts of osteotylus growth occurred to every animal in the young control group and their membrane bone formation was remarkable; comparatively, the osteotylus growth in the old group was weakened dramatically, and only fibrous joints were seen. The RT-PCR detection showed that differences of significance existed in both PPARγ and Cbfα1 mRNA expressions between the two groups, with the much higher Cbfol mRNA expression in the bone marrow of rats in the young group and the much higher PPARy mRNA expression in the bone marrow of rats in the old group.CONCLUSION: Rats of different ages show different fracture healing abilities, i.e. the higher ages, the lower fracture healing abilities. In addition, expressions of PPARγ and Cbfα1 in the bone marrow of rats alter with the increasing age, which indicates that there are certain associations between the changed expression level of the two factors and the fracture healing impartment.

Objective:Objectives The aim of the study is to evaluate the mechanical performance, safety and efficacy of the novel robotic-assistant flexible ureteroscopy system (Ra-fURS) under in vitro and in vivo environments.Methods:Combing with commercial flexible ureteroscopes, the novel Ra-fURS was used for the in vitro test and animal model operation in October 2020. The study included three sections. ①Basic mechanical performance assessment: including endoscope motion control (dual deflection, axial rotation and forward/backward distance), reaction time and fiber regulation. ②Simulated surgery in ex-vivo 3D-printing renal collecting system model: including completion rate and time of calyxes exploration, directional movement and laser fragmentation [gypsum models (0.5×0.5×0.5 cm) were used to stimulate kidney stones]. ③Intrarenal surgeries in animal models (two 5-month female Yorkshire white pigs). In total, 32 surgeries was performed (8 surgeons × 2 pigs × 2 kidneys/pig). In vivo assessments were carried out including: ①consuming time for Ra-fURS installation and offloading; ②completion rate and time of calyxes exploration; ③comfort score (ranging from 0-10) as compared to the manual f-URS, which was corresponding to each Ra-fURS surgery. In simulated surgery and animal surgery sections, 8 surgeons were enrolled in the study (group A 4 without flexible ureteroscopy experience; group B: 4 highly experienced), and results were compared between two groups.Results:Under the Ra-fURS control, the flexible ureteroscope movement in three degrees of freedom (forward / backward: + 11 to -11 cm, axial rotation + 225°to -225°; active duel-flection: + 270°to -270°, as well as the laser fiber regulation + 2.5 to -2.5 cm). In simulated surgery tests, both groups achieved 100% completion rate of calyxes exploration, and there were no statistical differences in the time of the calyxes exploration between group A and group B (116.0±8.0)s vs.(110.3±15.4)s( P>0.05). Time-consumption for laser fragmentation of group B was shorter than that of group A (525.8±58.5)s vs. (780.5±141.2)s( P<0.01). In animal surgery, the installation time of Ra-fURS gradually shortened within the first 7 cases was(234.0±43.0)s, and became comparable in the later 8-32 cases was(149.3±8.0)s. The average uninstall time was (43.9 ±5.9)s and was relatively stable. There were 51 renal calyxes in two pigs. It was higher for the completion rate of calyxes exploration in group B than in group A [(95.5±9.1)% vs. (59.1±9.1)%, P<0.05], and the exploration time was also statistically variant between the two groups group A and group B[(274.8±34.6)s vs.(127.3±18.2)s, P<0.05]. For all the operators, the comfort scores were favorable to the Ra-fURS as compared to the manual f-URS (8.9±0.3 vs. 5.9±1.1, P<0.05). Conclusions:This preliminary study demonstrated that the novel Ra-fURS was capable of controlling flexible ureteroscope to perform retrograde intrarenal surgery and fragmenting stones with laser. Besides, other features, including easy installation, stable performance and comfortable manipulating environment, made it easy to use in clinical application.

Objective: To summarize the initial experience of flexible ureteroscopy combined with thulium laser for the treatment of high-risk upper urinary tract urothelial carcinoma (UTUC) in patients with solitary kidney or renal insufficiency. Methods: A retrospective analysis was performed in 5 cases of UTUC with solitary kidney or renal insufficiency treated via flexible ureteroscopy combined with thulium laser from May 2016 to November 2018. Patients consisted of 4 cases of left side tumor, 1 case of right side tumor, with median age of 73 years old(ranging 53-87 years old). Among the 5 cases, 3 were solitary kidney with renal pelvis tumors, 2 cases were renal insufficiency accompanied with proximal ureter or renal pelvis tumor. All the patients had tumors large than 2 cm in diameter. The creatine in 3 cases with solitary kidney was 102, 128, 143μmol/L, respectively. The creatine in 2 cases with renal insufficiency was 281, 179μmol/L, respectively. Variable hydronephrosis was noticed in all paients. The cytological examination could reveal tumor cells in all cases. During the operation, part of tumor tissues were resected for pathological examination and the remaining visible tumor tissue was all ablated and vaporized. As there was no obvious residual tumor tissue, double J stent was retained. Patients were regularly reexamined after surgery. Results: Of the 5 cases, 4 patients were successfully performed, while intraoperative bleeding occurred in 1 case. The operation was suspended after indwelling double J stent. Then, the renal artery interventional embolism was performed after ineffective conservative treatment, and the bleeding was well controlled. One month later, the patient was treated with thulium laser tumor ablation and vaporizaiton under flexible ureteroscopy again. The pathology of all cases was high-grade invasive urinary epithelial carcinoma. Patients were followed up with regular imaging and endoscopic examination. The median follow-up period was 19 (4-26) months, during which 4 cases had local recurrence, one patient died of non-tumor factors. No recurrence of urothelial carcinoma occurred in the bladder during follow-up, the overall recurrence rate was 80%, and the median recurrence time was 6 (1-24) months. Patients with recurrence was treated with thulium laser tumor ablation and vaporizaiton under flexible ureteroscopy again. Conclusions Flexible ureteroscopy combined with thulium laser is an alternative treatment for high-risk upper urinary tract urothelial carcinoma in patients with solitary kidney or renal insufficiency, while with high tumor recurrence rate. Therefore, a stringent imaging and endoscopic follow-up should carry out postoperatively.

Objective To study the effect of diffusion-weighted magnetic resonance imaging (DW-MRI) in the differential diagnosis of hydronephrosis and pyonephrosis.Methods From March 2015 to October 2017,50 patients with renal stone and highly suspected infectious hydronephrosis underwent renal DW-MRI,and clinical materials were collected and analyzed retrospectively.Seventeen male and 33 female patients were enrolled with a mean age of (49.40 ±-10.51) years.The median maximum diameter of renal stone was 30.30 (17.38,56.01) mm and hydronephrosis was 46.39 (34.33,56.55) mm.No pyonephrosis was diagnosed by preoperative ultrasound or CT,while 29 cases of hydronephrosis and 21 cases of pyonephrosis were reported by preoperative DW-MRI.Final diagnoses of hydronephrosis and pyonephrosis were made according to whether the pelvic urine drainage was purulent or not during the surgery.DW-MRI reports and characteristics of DW images were analyzed retrospectively.Apparent diffusion coefficient (ADC) was calculated and ADC map constructed,which was compared between the two groups.Receiver operating characteristic curve (ROC) was drawn to analyze the area under curve (AUC) and the optimal cutoff of ADC value,with sensitivity and specificity.Results Thirty-three patients of hydronephrosis and 17 pyonephrosis were confirmed intraoperatively.The overall accuracy of diagnosis using DW-MRI was 84.00％ (42/50),with sensitivity of 88.24％ (15/17) and specificity of 81.82％ (27/33).Among 30 patients who underwent CT scan in our hospital,mean CT value of 18 hydronephrosis was (7.03 ± 3.26)HU and that of 12 pyonephrosis was (8.67 ± 3.52) HU,with no statistical significance (P ＞ 0.05).On DW image,when b ≥ 500 s/mm2,hydronephrosis signal intensity was lowered apparently,whereas pyonephrosis signal intensity was intensified.On ADC map,hydronephrosis appeared as hyperintensity,whereas pyonephrosis appeared as hypointensity.The mean ADC value of pyonephrosis group was lower than hydronephrosis group [(1.53 ±0.58) × 10-3 mm2/s vs.(2.86 ±0.56) × 10-3 mm2/s,p ＜0.01].ROC analysis revealed that AUC =0.92 (95％ CI 0.80-0.98),and the cut-off value of ADC for pyonephrosis diagnosis was 1.39 × 10-3 mm2/s,of which the sensitivity and specificity was 94.12％ and 84.85％ respectively.Conclusions Signal of pyonephrosis was enhanced on DW image,while decreased on ADC image.The ADC value of pyonephrosis was much lower than that of hydronephrosis,with which the differential diagnosis between pyonephrosis and hydronephrosis could be made efficiently.

Objective:To discuss the regulatory effect of berberine(BBR)on fatty acids in the human glioma T98G cells and its effect on the cell proliferation,migration,and invasion,and to clarify its potential mechanism.Methods:The T98G cells at logarithmic growth phase were divided into control group and different concentrations(25,50,and 100 mg·L-1)of BBR groups.Cell wound healing assay was used to detect the migration rates of the cells in various groups;Transwell chamber assay was used to detect the invasion rates of the cells in various groups.The T98G cells at logarithmic growth phase were divided into control group and 100 mg·L-1 BBR group,and Mass spectrometry was used to detect the fatty acid contents in the cells in two groups.The T98G cells at logarithmic growth phase were divided into control group and different concentrations(50,100,and 150 mg·L-1)of BBR groups;Western blotting method was used to detect the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(AKT),phosphorylated AKT(p-AKT),sterol regulatory element-binding protein 1(SREBP-1),and fatty acid synthase(FASN)in the cells in various groups.The expression of FASN was suppressed by gene silencing technology,and the T98G cells at logarithmic growth phase were divided into control group,shFASN1 group,and shFASN2 group.Western blotting method was used to detect the expression levels of FASN protein in the cells in various groups;clone formation assay was used to detect the clone formation of the cells in various groups;cell wound healing assay was used to detect the migration rates of the cells in various groups.Results:Compared with control group,the migration rates and invasion rates of the cells in different concentrations of BBR groups were decreased in a concentration-dependent manner(P<0.01),and the fatty acid content in the cells in 100 mg·L-1 BBR group was significantly decreased(P<0.01).Compared with control group,the expression levels of p-PI3K,p-AKT,SREBP-1,and FASN proteins in the cells in 150 mg·L-1 BBR group were significantly decreased(P<0.05 or P<0.01),and the expression level of SREBP-1 protein in the cells in 100 and 150 mg·L-1 BBR groups were significantly decreased(P<0.01).After suppression of FASN expression,compared with control group,the expression levels of FASN protein in the cells in shFASN1 and shFASN2 groups were significantly decreased(P<0.01),and the expression level of FASN protein in the cells in shFASN2 group was lower than that in shFASN1 group(P<0.05);compared with control group,the numbers of clone formation and migration rates of the cells in shFASN1 and shFASN2 groups were significantly decreased(P<0.01),and the migration rate of the cells in shFASN2 group was significantly lower than that in shFASN1 group(P<0.05).Conclusion:BBR interferes with fatty acid synthesis in the glioma T98G cells by reducing the expression of the PI3K/AKT/SREBP-1/FASN pathway related proteins,and decrease their migration and invasion capabilities.

Objective:To explore the impact of clinical features, serological indicators, and pulmonary function test (PFT) on the prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD).Methods:Clinical data of RA-ILD patients who were diagnosed by HRCT and were followed up in Changhai Hospital or Yancheng First People's Hospital from 2011 to 2021 were collected Respiratory functional impairment of the patients was evaluated according to the changes of HRCT score and PFT, and the patients were divided into progressive group and stable group. COX survival analysis and ROC curve were used to determine the factors related to the progression of RA-ILD.Results:Finally 98 RA-ILD patients were included. The mean age of ILD onset was (62.9±12.1) years old, the median course of RA was 7.0 (1.0, 15.3)years, and the median follow-up time was 36.5 months (14.0, 79.5). There were 49 cases in the progressive group, and the clinical characteristics and laboratory tests of the two groups were compared. The results showed that: progressive time [(23(8.5,43.0)months vs 63(32.5,90.9) months, Z=-4.55, P=0.001)], HRCT score [(115(109,135) vs 111(105,116), Z=-2.70, P=0.007)], forced vital capacity(FVC) predicted [(70.1±15.7)% vs (80.8±19.7)%, t=2.12, P=0.039)], diffusing capacity of the lungs for CO(DLCO) predicted [(57.5±16.3)% vs (83.4±18.8)%, t=4.87, P=0.001)], male [(44.9% vs 18.4%, χ2=7.97, P=0.005)], UIP pattern [(36(73.5%) vs 9(18.4%), χ2=29.96, P<0.001)], RF>200 U/ml[(21(65.6%) vs 18(41.9%), χ2=4.15, P=0.042)], anti-CCP>75 U/ml [(42(91.3%) vs 35(71.4%), χ2=6.10, P=0.013], all had significantly different between the two groups. In multivariate analyses, UIP[ HR(95% CI)=3.25(1.62,6.50), P<0.001], anti-CCP antibody >75 U/ ml[ HR(95% CI)=3.85 (1.20,12.33), P=0.023] and smoking [ HR (95% CI): 5.74(1.10, 30.13), P=0.039] were significantly correlated with the progression of pulmonary fibrosis in RA-ILD patients. PFT was performed in only 44 patients with RA-ILD. The univariate analyses and ROC curve suggested that DLCO predicted [ HR (95% CI)=1.04 (1.02,1.06), P<0.001] was a significant risk factor for the progression of RA-ILD, and the area under curve (AUC) of DLCO was 0.845 [95% CI=(0.729,0.961)]. Conclusion:UIP pattern, high titer of anti-CCP antibody, smoking, and reduced DLCO predicted % may be potential predictors for poor prognosis of RA-ILD patients.

Objective:To investigate the effectiveness and safety of nasojejunal tube placement in children by gastroscopic drafting method.Methods:We retrospectively analyzed the clinical data of children with nasojejunal tube placement from January 2016 to December 2021 in our hospital, and compared the operation time, successful rate and complications of nasojejunal tube placement in the gastroscopic wire drawing method retraction group(observation group)and the gastroscopic foreign body clamp placement method placement group(control group).Results:All of the 167 cases, 65 cases were in observation group and 102 cases in control group.There were no significant differences in sex and age between two groups( P>0.05). The operation time was(6.7±0.8)min in observation group and(8.2±1.3)min in control group, and the difference was statistically significant( t=8.312, P<0.001). The successful rate was 100% in observation group and 96% in control group.One child in control group complicated with the mucosal erosion and bleeding in the duodenal bulb, while the observation group with no erosion, bleeding, perforation, and other complications. Conclusion:The gastroscopic wire drawing method of nasojejunal tube placement has a shorter operation time, higher successful rates, and lower complication rates, which is significantly superior to the gastroscopic foreign body clamp placement method.