Objective: To optimize the formula and preparation technology of cantharidin chitosan bioadhesive microspheres.Methods: The microspheres were prepared by a spray drying method.A single-factor experiment was used to study the effect of chitosan with different molecular weight on the gastric mucosa adhesion rate were also studied, and the effects of different drug loading ratio, concentration of chitosan acetic acid solution and speed of peristaltic pump on the loading rate were also studied.The cantharidin entrapment efficiency as the studying index, a response surface method was used to further optimize the formula.Results: The best formula and preparation process of cantharidin chitosan bioadhesive microspheres were as follows: the concentration ratio of antharidin to chitosan was 19.83% , the concentration of chitosan acetic acid solution was 0.77% , and the peristaltic pump flow rate was 9.225 ml·min-1.With the best formula, the entrapment efficiency of cantharidin chitosan bioadhesive microspheres was 90.14%.Conclusion: The microsphere preparation by the spray drying method is stable and repeatable.Cantharidin chitosan bioadhesive microspheres have high entrapment efficiency and promising biological adhesion.

Cell-penetrating peptides (CPPs) offer a non-selective and receptor-independent mode to promote cellular uptake. Although the non-specificity of CPP-mediated internalization allows this approach applicable to a wide range of tumor types potentially, their universality is a significant obstacle to their clinical utility for targeted delivery of cancer therapeutics and imaging agents. Accordingly, many reports have focused on selective switching of systemically delivered inert CPPs into their active form in lesions (tumor). In this review, our attention is mainly confined to such an enzyme-sensitive domain incorporated delivery system with activatable CPPs (ACPPs), which have displayed the exciting strength in balancing the CPPs' pros and cons, and potential in the treatment and diagnosis of some diseases.

Objective To evaluate the diagnostic value of the aldosterone-renin ratio (ARR) for primary aldosteronism (PA). Methods Serum aldosteronos ( ALD ) and plasma renin activities (PRA)among 44 subjects with primary aldosteronism, 9 subjects with phecchromocytoma, 8 subjects with nonfunctional adrenal tumors, 12 subjects with Cushing syndrome, 4 subjects with stenosis of renal artery and 13 subjects with primary hypertension were retrospectively reviewed. ARR was calculated. The receiver operating characteristics (ROC) curves for every index were used to evaluate diagnostic value. Results The area under the curve(AUC) in the ROC curve of ALD in a supine position was 0. 947, the cut-off value of diagnosis of PA. The AUC for the ROC curve of ALD in upright position was 0. 889, the cut-off value of ALD diagnosis of PA. The AUC for the ROC curve of ARR in a supine position was 0. 978, the cut-off value of diagnosis of PA. The AUC for the ROC curve of ARR in upright position was 0. 981, the cut-off value of specificity. If ARR was combined with ALD in upright position was used, the diagnostic value was better than either index. When ALD > 275 ng/L and the AUC for the ROC curve in upright position was 0. 989,specificity. Conclusions The diagnostic value of ARR in diagnosis of primary aldosteronism is higher than ALD and PRA. ARR in upright position is better than that in supine position, especially when combined with ALD > 275 ng/L in upright position.

Objective:To find out predictors of the testicular ischemia caused by incarcerated inguinal hernia and evaluate the ischemic injury of the testis more accurately, which can indicate testicle exploration in time or prevent unnecessary testicle exploration.Methods:Pediatric patients (median: 9 months) undergoing operation of unilateral incarcerated inguinal hernia and ipsilateral testicular exploration from 1 Jul. 2013 to 30 Jun. 2019 were retrospectively investigated. Age at surgery, incarcerate duration, degree of intestinal and testicular injury, times of manual reduction and preoperative ultrasound data were collected. Statistical analysis was performed by SAS 9.4 (Copyright ? 2016 SAS Institute Inc.Cary, NC, USA) .Results:460 patients (median: 9 months) , of which 57 (12.39%) (median: 1.4 months, interquartile range 0.8-10.7 months) had severe testicular injury, and their average incarceration time was (23.9±9.3) h. Univariate logistic regression revealed that increased times of manual reduction, ultrasound scores, incarcerate duration and degree of intestinal injury were positively correlated with the degree of testicular ischemia, while age at surgery was negatively correlated with the degree of testicular ischemia ( P<0.05) . A model for calculating the probability of severe testicular ischemia injury was established: P= through multivariate analysis with backward stepwise logistic regression and 10-fold cross-validation was used for preliminary verification of the model. Conclusion:This study provides a relative reliable model to predict the risk of irreversible testicular ischemia due to incarcerated inguinal hernia using readily available clinical characteristics in young pediatrics with testicular ischemia.

Objective To analyze the frequency of pelvis peristalsis in children with hydronephrosis and its correlation with postoperative percentage of improvement in anteroposterior diameter (PI－APD).Methods From Oc-tober 2015 to September 2017,the data of the children with unilateral ureteropelvic junction obstruction (UPJO)hydro-nephrosis who underwent laparoscopic pyeloplasty were collected,and their pelvis peristalsis frequencies of 2 min were recorded after exposing the pelvis,while the APD and PI－APD were followed 1 year posto-peratively.The degrees of hydronephrosis were divided into mild,moderate and severe according to the Society of Fetal Urology(SFU)classifica-tion system.ANOVA was used to compare the pelvis peristalsis frequency and postoperative PI－APD between different degrees of hydronephrosis.Spearman analysis was used to analyze the correlation between pelvis peristalsis frequency and degree of hydronephrosis.Meanwhile,Pearson test was used to analyze the correlation between pelvis peristalsis fre-quency,hydronephrosis degree and PI－APD.Results A total of 50 children were included,of which 36 patients got follow－up for 1 year postoperatively.Pelvis 2 min peristalsis frequency between different degrees of hydronephrosis [mild:(8.1 ± 3. 3)times;moderate:(6.3 ± 3.5)times;severe:(7.8 ± 3.9)times]had no significant difference (F＝0.65,P＝0. 527);no statistical correlation was observed between pelvis peristalsis frequency and degree of hydro-nephrosis or PI－APD (all P ＞0.05).Preoperative hydronephrosis degree was positively correlated with PI －APD (r＝0.54,P＝0. 001).PI－APD in severe hydronephrosis (0.48 ± 0.29)was significantly higher than that of mild hydronephrosis (0.21 ± 0.20)(P ＝0.001 ). Conclusions For children with different degrees of hydronephrosis caused by UPJO,there was no significant difference in the pelvis peristalsis frequency recorded during laparoscopic pyeloplasty.Pelvis peristalsis frequency recorded during surgery was not correlated with PI －APD,but preoperative hydronephrosis degree was positively correlated with postoperative PI－APD.

OBJECTIVETo observe the histological features of tumor-bearing tissues formed by human fibroblasts after reprograming by spermatogonial stem cell self-renewal key regulating gene Piwil2 (Piwil2-iCSC).

METHODSPiwil2-iCSC tumor spheroids-like colonies were selected for tumor formation assay in four nude mice. Pathological features of Piwil2-iCSC tumors were observed by histology. Stem cell markers and common triploblastic markers were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) assay and immunohistochemistry. Germ cell tumor markers were detected by immunohistochemical examination.

RESULTSTwo weeks after inoculation, subcutaneous tumors were formed in all the four nude mice with a tumor formation rate of 100%. In the Piwil2-iCSC tumor tissues, Piwil2-GFP(+) cells showed high-density nuclear expression and were widely observed in DAPI-stained sections. Numerous mitotic figure of the neoplastic cells were seen (>10 cells/field of vision under high magnification) in HE-stained sections. Enlarged abnormal cell nuclei were observed. RT-PCR assay showed that Piwil2-iCSC tumors still expressed Piwil2 and some self-renewal and pluripotent markers of stem cells and some markers of triploblastic differentiation. Immunohistochemical staining showed that the tumors expressed stem cell markers, triploblastic markers and germ cell tumor markers AFP and HCG.

CONCLUSIONSPiwil2-iCSC tumors are probably undifferentiated embryonic small cell carcinoma, most likely to be immature teratoma, mixed with yolk sac tumor and choriocarcinoma components. It can be used as a useful model for the research of origin or genesis mechanism of cancer stem cells and the treatment of relevant tumors.

Adult Stem Cells ; Animals ; Argonaute Proteins ; genetics ; Cellular Reprogramming Techniques ; Choriocarcinoma ; pathology ; Endodermal Sinus Tumor ; pathology ; Fibroblasts ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Mice ; Mice, Nude ; Neoplasms, Germ Cell and Embryonal ; chemistry ; genetics ; pathology ; Neoplastic Stem Cells ; chemistry ; pathology ; Real-Time Polymerase Chain Reaction ; Spheroids, Cellular ; Teratoma ; pathology ; Time Factors

Objective To evaluate the observation period and association between the initial visit data including initial APD measured by ultrasonography (USG) and outcome of unilateral hydronephrosis caused by ureteropelvic junction obstruction (UPJO) in children.Methods One hundred and ninety-three children with UPJO,who underwent the USG at the initial visit time.There were 155 boys and 38.166 cases in left side and other 27 cases in right side.All cases were divided by initial visit time and initial APD respectively.There were 109 infancy(≤ 12 months),36 toddler(12-36 months),19 preschooler(36-60 months),29 school-age children(＞ 60 months)and 11 cases in normal group (APD ＜ 0.5 cm),47 in mild (0.5 cm≤APD ＜ 1.0 cm),54 in moderate(1.0 cm≤ APD≤ 1.5 cm),81 in sever(APD ＞ 1.5 cm).All the patients were follow up for at least 24 months and divided into two groups depended on whether the patients received the surgery.Results Areas under the receiver operating characteristic plots were 0.924 (95％ CI 0.870-0.977,P ＜ 0.01);sensitivity,specificity,positive predictive value,and negative predictive value were 87.2％,88.9％,87.5％,and 95.5％,respectively,for the cut of APD is ≥ 1.85 cm.Infancy and initial APD ＞ 1.5 cm was the risk factors predicting operation with the hazard ratio of 2.991 (95％ CI 1.328-6.734,P =0.008) and 16.593 (95％ CI 5.893-46.719,P ＜ 0.01),respectively.Operation rate at one year of UPJO,for initial APD ＞ 1.5 cm,initial APD ≤ 1.5 cm,infancy and after infancy,were 43.20％(35/81),2.67％ (3/112),30.27％ (33/109),5.95％ (5/84),respectively.Conclusions Initial USG is an efficient diagnostic tool to detect pathologic hydronephrosis.Initial APD predicts the clinical outcome of UPJO in pediatrics accurately.Further investigation is recommended when initial APD ＞ 1.5 cm.Close observation is needed during the one year after initial visit to detect the deterioration of UPJO,especially in infancy.

Objective:To discuss the diagnosis and treatment of ectopic ureter company with the bladder neck and urethral maldevelopment in children.Methods:The clinical data of the 6 patients admitted to Children’s Hospital affiliated to Chongqing Medical University from September 1993 to April 2019 diagnosed as ectopic ureter company with the bladder neck and urethral maldevelopment were retrospectively reviewed. The 6 children were girls and the median age was 7 years old , ranged from 2 to 15 years old. All children had ectopic ureter, including 3 in left-sided, 1 in right-sided, and 2 in bilateral-sided. Five children presented the intermittent dribbling incontinence and one child presented the continuously incontinence without normal voiding. Through ultrasound, IVP, MRI, cystoscopy and retrograde urography, seven ureters were found ectopic position, including bladder neck in 4 cases, two ureters inserted in the vagina in 2 cases. There were two cases with duplex kidney and 4 cases with renal dysplasia. Preoperative cystoscopy revealed wide and short urethra in 1 case, wide bladder neck combined with wide and short urethra in 4 cases. The surgery type included nephrectomy in cases 1-3, bilateral ureter reimplantation in case 4 who had the bilateral ectopic ureter , bilateral ureter reimplantation and bladder neck reconstruction at the same time in case 5. Nephrectomy associated with bladder neck and urethral reconstruction in case 6.Results:Five patients were followed-up and one patient was lost to follow-up after the first operation. Mean follow-up was 41.2 months (ranging 2 to 84 months). Four patients with bladder neck and maldevelopment that were not solved intraoperatively got reoperations due to incontinence without remission. Case 1, who underwent urethral reconstruction and extension, and urinary incontinence was partially relieved. Case 2 was found to have wide bladder neck deformity, and then retrospectively got bladder neck reconstruction and urethrovaginal fistula repair in 3 years and 5 years later. The urinary incontinence was completely relieved. The ureteral stump of case 3 was resected 2 years after operation due to recurrent urinary tract infection, and then got twice bladder neck and urethral reconstruction in 3 years and 6 years later of nephrectomy. His incontinence was partially relieved. The case 4 got bladder neck and urethral reconstruction in one year after bilateral ureter reimplantation, and incontinence was partially relieved too. Among the two patients underwent combined surgery, the case 5, who got bilateral ureteral bladder replantation combined with bladder neck reconstruction, were lost to follow-up after surgery. The case 6 got dysplasia nephrectomy combined with bladder neck reconstruction and urethroplasty were completely relieved of urinary incontinence.Conclusions:Bladder neck and urethra maldevelopment is one of the main causes of urinary incontinence after surgery in children with ectopic ureter. The diagnosis mainly relies on cystoscopy. The treatment mainly relies on surgery. Bladder neck and urethral reconstruction is expected to be available. If the operative conditions permit, synchronous surgical treatment of ectopic ureter and bladder neck and urethral maldevelopment will get a better prognosis than staging surgery.

Objective To study the vascular anatomy of duplex kidney and to provide a scientific basis for surgical resection of the renal segment.Methods From February 2012 to April 2018,the clinical data of 84 children with renal duplex kidney disease admitted to our hospital,were reviewed and analyzed.Among them,75 cases (89.3％) were unilateral and 9 cases (10.7％) were bilateral.According to the preoperative CT + CTA and the duplicated renal morphology,size,location,and anatomical relationship of the kidney segment,combined with the branches and passage of the renal artery which supplies the upper moiety,it described the blood supply of the upper renal moiety.At the same time,it analyzed various types of embryological related factors and gender differences and summarized the tips for laparoscopic surgery.Results Of the 93 duplex kidneys,69 (74.2％) were supplied with 1 artery,and 25 (26.9％) were supplied with 2 or more arteries.Based on the shape and orifice of artery,they were divided into 3 types.The most common type was that the renal artery separated into two or more arteries near the renal parenchyma.The upper and lower renal poles were respectively supplied,which could be summarized as early branching,a total of 71 sides (76.3 ％).The second type was the arteries from abdominal aorta or its branches,directly flowing into the upper renal pole,which was classified into the sub-renal artery,a total of 18 sides (19.4％).The others (4 sides,3.3％) were less common,and most of them were a combination of the above-mentioned two types,and one of them whose upper pole was supplied by branches of adrenal artery.Based on the classification of vascular variability,no significant difference was found between males and fenmals,or left and right sides.Conclusions The upper renal moiety are mainly supplied by one branch of renal artery,and the most common type of this artery is prehilar branch,without gender difference.The determination of vascular variability before surgery can avoid bleeding during surgery and avoid accidental injury of normal blood vessels.

OBJECTIVE: To investigate the transcriptome profile of genital tubercles (GTs) in male SD rats and explore the mechanism of hypospadias induced by Di (2-ethylhexyl) phthalate (DEHP). METHODS: Forty time-pregnant SD rats were randomly divided into 4 equal groups, namely GD16 group and GD19 group (in which the male GTs were collected on gestation day[GD]16 and GD19 for RNA-seq, respectively), control group and DEHP exposure group (with administration of oil and 750 mg/kg DEHP by gavage from GD12 to GD19, respectively).In the control and DEHP exposure groups, the GTs were collected from the male fetuses on GD19.5, and scanning electron microscopy and HE staining were used to observe the morphological changes.The differentially expressed genes (DEGs) in the GTs were screened using lllumina HiSeq 2000 followed by GO and KEGG enrichment analyses to characterize the transcriptome profile.Immunofluorescence assay was performed to verify the DEGs (Mafb) identified by RNA-seq results.Immunofluorescence assay and Western blotting were used to examine the expression levels of Mafb in the penile tissue. RESULTS: A total of 1360 DEGs were detected in the GTs between GD16 group and GD19 group by RNA-seq.Among these genes, 797 were up-regulated and 563 were down-regulated.These DEGs were mainly enriched in the cell adhesion plaque signaling pathway, axon guidance signaling pathway, and extracellular matrix receptor signaling pathway.Compared with that in GD16 group, Mafb was significantly up-regulated in GD19 group, which was consistent with the sequencing results.Mafb and β-catenin were significantly down-regulated in DEHP-exposed group compared with the control group ( < 0.01). CONCLUSIONS Mafb expression increases progressively with the development of GTs in male SD rats.DEHP exposure causes significant down-regulation of Mafb and β-catenin, suggesting that β-catenin signaling pathway that affects Mafb is related to DEHP-induced hypospadias in SD rats.
Animals ; Diethylhexyl Phthalate ; Female ; Gene Expression Profiling ; Humans ; Hypospadias ; MafB Transcription Factor ; Male ; Oncogene Proteins ; Phthalic Acids ; Pregnancy ; Rats ; Rats, Sprague-Dawley