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Conventional gels manifest monotonous swelling or shrinking performance upon immersing in solvents until reaching an equilibrium state. Recently, we discovered that the “hydrophobic hydrogels” prepared from hydrophobic polymer networks demonstrated dynamic swelling performance without equilibrium states. Upon water immersion, the gels expanded tremendously at the first stage until reaching a swelling peak; subsequently, the gels shrunk at an extremely slow rate. While this phenomenon endows the material with an unusual feature, more efforts are highly demanding for the full understanding of this performance. Herein, we systematically investigate the hydrophobic hydrogels’ swelling kinetics by screening the organic solvent dependence, polymer effect, and temperature impact. It is revealed that the chemical structure of gels greatly influences the swelling kinetics. The higher the networks’ hydrophobicity, the slower the swelling kinetics. Meanwhile, organic solvents demonstrate a limited effect on the dynamic swelling performance. Moreover, higher temperature significantly accelerates the whole volume change process. Based on the swelling performance, we further develop hydrogel-based soft devices with time-programmable two-dimensional and three-dimensional shape-shifting performances.

Nature consists of various soft tissues with well-ordered hierarchical anisotropic structures, which play essential roles in biological systems to exhibit particular functions. Mimicking bio-tissues, synthetic hydrogels with anisotropic structures have received considerable attention in recent years. However, existing approaches to fabricate anisotropic hydrogels often require complicated procedures, which are time-consuming and labor-demanding. Inspired by the dry-induced crystallization phenomenon, we report a simple yet effective prestretching-drying-swelling method to afford anisotropic crystalline polyvinyl alcohol hydrogels. Owing to the distinct anisotropic microstructure, the hydrogels demonstrate excellent mechanical properties with noticeable directional distinction. It is revealed that both the enhancing of pre-orientation strain and the extending of heating time make the hydrogels with better mechanical properties and more remarkable anisotropicity. Owing to the anisotropically aligned structure, the hydrogels exhibit remarkably differential ionic conductivity: the difference between the parallel and vertical conductivity of the same sample can reach as high as 6.6 times, making the materials possible candidates as nano-conductive materials. We anticipate that this simple yet effective approach may become highly useful for fabricating oriented hydrogels and endow the materials with more promising application prospects in the future.

Aldosterone exerts an enormous function on proximal tubular cells (PTC) senescence, which is a common pathomechanism contributing to renal dysfunction. Numerous studies have shown that oxidative stress is deeply involved in the pathophysiologic processes of chronic kidney diseases. The study aims to investigate whether autophagy could regulate the process of senescence through oxidative stress in PTC both in vivo and ex vivo. Our results suggested that aldosterone treatment increased the senescence and oxidative stress as evidenced by increased percent of SA-β-Gal positive cells, reactive oxygen species level, expression of NADPH oxidase 4 (NOX4) rather than NOX2, and the up-regulation of p21 in cultured PTC. Furthermore, the alternation of the expression of p62 and LC3-II/LC3-I demonstrated that aldosterone treatment remarkably influenced autophagic flux. NOX4 siRNA treatment or autophagy induction with rapamycin reduced the oxidative stress and senescence in aldosterone-induced PTC. On the contrary, inhibition of autophagy with chloroquine worsened these changes. Similar results were further confirmed in vivo. Our results suggested that autophagy may become a realistic therapeutic strategy against aldosterone-induced PTC injury via improving oxidative stress.

Foot process effacement is an important feature of early diabetic nephropathy (DN) which is closely related to the development of albuminuria. Under certain nephrotic conditions, the integrity and function of the glomerular slit diaphragm (SD) structure were impaired and replaced by the tight junction (TJ) structure, resulting in so-called SD-TJ transition, which could partially explain the effacement of foot processes at the molecular level. However, the mechanism underlying the SD-TJ transition has not been described in DN. Here, we demonstrated that impaired autophagic flux blocked p62 mediated degradation of ZO-1 (TJ protein) and promoted podocytes injury via activation of caspase 3 and caspase 8. Interestingly, the expression of VDR in podocytes was decreased under diabetic condition which impaired autophagic flux through down-regulating Atg3. Of note, we also found that VDR abundance was negatively associated with impaired autophagic flux and SD-TJ transition in the glomeruli from human renal biopsy samples with DN. Furthermore, VDR activation improved autophagic flux and attenuated SD-TJ transition in the glomeruli of diabetic animal models. In conclusion, our data provided the novel insight that VDR/Atg3 axis deficiency resulted in SD-TJ transition and foot processes effacement via blocking p62-mediated autophagy pathway in DN.

Soft tissue engineering requires antifouling materials that are biocompatible and mechanically flexible. Conventional hydrogels containing more than 70 wt% water are thus promising antifouling material candidates. However, some hydrogels are difficult to apply in internal body organs because of undesirable protein absorption on their surfaces. Due to the lack of an effective method for observing the true charge densities of hydrogels, the reason why electrostatic interactions dominate protein absorption behavior remains unclear. In this work, we adopt the microelectrode technique (MET) to study the electrical potentials of hydrogels with negative, positive, and neutral potentials and demonstrate the protein absorption behaviors on those hydrogels. The results show that MET is an effective method to obtain the surface charge densities of various hydrogels. Furthermore, the amounts of absorbed proteins on the gels were quantified with respect to the charge densities of the hydrogels. The results indicate that electrostatic absorption is quantitatively dominated by a combination of hydrogel charge density and overall protein charge. Based on the knowledge obtained in this work, the effects of hydrogel surface charges on protein absorption can be better understood. Thus, the results are expected to promote the application of hydrogels in tissue engineering.

The role of glucagon-like peptide-1 analog (GLP-1) in autophagic flux and lysosomal dysfunction in obesityrelated glomerulopathy (ORG) remains poorly understood. Here, we demonstrated that exposure to a high-fat diet (HFD) resulted in ectopic lipid accumulation, increased 24-hour urinary albumin, and vacuolated tubular cells. The apoptotic cell content in renal tubules was remarkably increased in the HFD group, compared to CON mice, as evident from TUNEL staining and caspase-3 expression, and significantly decreased upon switching to the normal chow diet and GLP-1 treatment. Compared to the control group, significant accumulation of Oil red O staining and CD36 and PLIN2 was observed in tubular cells of HFD mice. In the HFDG and HFD-C groups, lipid droplet deposition in tubular cells were inhibited. LC3 and p62 levels were markedly increased in proximal tubules of HFD mice, and palmitic acid impaired autophagic flux in HK2 cells. Electron microscopy revealed that non-functional lysosomal residue merged with the functional lysosome in the HFD group. GLP-1 treatment and a normal chow diet led to inhibition of enlarged lysosomal residue and restored autophagic flux. In conclusion, impaired lysosome and autophagic flux may be ameliorated by GLP-1 treatment and replacement with a normal chow diet.

There is huge shortage of ERCP practitioners (ERCPists) in China, and ERCP training is urgently needed. ChangHai Advanced eNdoscopy Courses for ERCP (CHANCE) is a 4-month program for ERCP training since 2004. This study evaluated the efficiency of this short-term training model, and reported on the ERCP careers of the trainees following completion of the CHANCE program.This study was a retrospective investigation included all the CHANCE trainees from Jan 2004 to Dec 2014. Questionnaires were sent to all trainees. The career competence percentage, ERCP careers and predictive factors of career competence were investigated and analyzed.A total of 413 trainees participated in the CHANCE program over 11 years covered by the survey and 258 questionnaires were valid for the study. The mean (SD) age of the trainees was 35.36 (4.17), and the male to female ratio was 4.4:1. The average follow-up time was 7.77 (3.44) years. A total of 173 (67.1%) trainees had achieved career competence. In terms of ERCP careers, the mean annual ERCP volume was 120.60 (96.67), with a complication percentage of 8.2%. Hospital qualification, compliance with follow-up learning guidance, participating academic activity, and practitioner type were identified predictive factors of career competence.As a short-term training program, the CHANCE achieved an acceptable career competence percentage, providing endoscopists more chances to learn ERCP and giving them appropriate training guidance for career competence. This training mode is worth promoting in developing countries with shortage of ERCPists.

OBJECTIVE The study concerns identifying risk factors and developing nomogram for pancreatic pseudocyst (PPC) in idiopathic chronic pancreatitis (ICP) to facilitate early diagnosis. METHODS From January 2000 to December 2013, ICP patients admitted to our center were enrolled. Cumulative incidence of PPC was determined by Kaplan-Meier method. Patients were randomized into training group and validation group in a 2:1 ratio. Risk factors of PPC were determined through Cox proportional hazards regression model based on training cohort. The nomogram was constructed according to risk factors. RESULTS Totally, 1633 ICP patients were included with a median follow-up duration of 9.8 years. Pancreatic pseudocyst was observed in 14.7% (240/1633) of patients after ICP onset. The cumulative incidences of PPC were 8.2%, 10.4%, and 12.9% at 3, 5, and 10 years after ICP onset, respectively. Male sex, smoking history, history of severe acute pancreatitis, and chronic pain at/before diagnosis of ICP and complex pathologic changes in main pancreatic duct were recognized as risk factors of PPC development. The nomogram constructed with these risk factors achieved good concordance indexes. CONCLUSIONS Risk for PPC could be estimated through the nomogram. High-risk patients were suggested to be followed up closely to help early diagnosis of PPC.

Bimodal classification of idiopathic chronic pancreatitis (ICP) into early-onset (35 years) ICP was proposed in 1994 based on a study of 66 patients. However, bimodal distribution wasn’t sufficiently demonstrated. Our objective was to examine the validity and relevance of the age-based bimodal classification of ICP. We analyzed the distribution of age at onset of ICP in our cohort of 1633 patients admitted to our center from January 2000 to December 2013. Classify ICP patients into early-onset ICP(a) and late-onset ICP(a) according to different cut-off values (cut-off value, a = 15, 25, 35, 45, 55, 65 years old) for age at onset. Compare clinical characteristics of early-onset ICP(a) and late-onset ICP(a). We found slightly right skewed distribution of age at onset for ICP in our cohort. There were differences between early-onset and late-onset ICP with respect to basic clinical characteristics and development of key clinical events regardless of the cut off age at onset i.e. 15, 25, 35, 45 or even higher. The validity of the bimodal classification of early-onset and late-onset ICP could not be established in our large patient cohort and therefore such a classification needs to be reconsidered.

The extreme mechanical strength of fibrous connective tissues in the human body, such as ligaments and tendons, has always been challenging for hydrogel scientists. Here, we created extremely strong, purely cellulose-based hydrogels (DCC-E gels). The fracture stress and Young’s modulus of the gels were improved to the level of an Achilles tendon even at their equilibrium swollen state. To make DCC-E gels, regenerated cellulose gels were first prepared with ethanol as the anti-solvent. DCC-E gels were then prepared by applying Drying in Confined Condition method, where regenerated cellulose gels were prestretched and dried while their length was fixed. Although strength improvement of materials is typically only achieved at the expense of toughness, a significant increase in strength was achieved while maintaining high levels of toughness. The high strength and toughness of the DCC-E gels were realized by optimizing the cellulose fibril arrangement from nanoscale to macroscale, which was done by selection of an appropriate solvent used for cellulose regeneration. Parallel aggregated fibrous structures observed in the DCC-E gels are thought to play a central role in the enhancement of both toughness and strength. This study can assist in expanding the application of biopolymer-based hydrogels in tissue engineering and soft electronics.

Pediatric patients suffer from chronic pancreatitis (CP), especially those with diabetes mellitus (DM). This study aimed to identify the incidence of and risk factors for DM in pediatric CP. CP patients admitted to our center from January 2000 to December 2013 were assigned to the pediatric (

Chronic pancreatitis (CP) is characterized by persistent inflammation and fibrosis of the pancreas. To date, no clinical therapy is available to reverse the inflammatory damage or pancreatic fibrosis associated with CP. This study systematically investigated the effect of Dasatinib, a multiple tyrosine kinases (TKs) inhibitor, on pancreatic fibrosis and inflammation in vivo and in vitro. We found that Dasatinib notably ameliorated pancreatic fibrosis and infiltration of macrophages in a model of caerulein-induced murine CP. Further RNA-seq and phosphoproteomic analysis and in vitro validation assays indicated that Dasatinib exerted a marked inhibition on the proliferation and activation of PSCs, which may be resulted from increased GSK3β-mediated β-catenin cytosol retention by inhibiting upstream multiple TKs (such as PDGFR and Src) and MAPK cascades (including ERK1/2 and p38 MAPK). In addition, Dasatinib significantly restrained both the M1 and M2 polarization of macrophages, and impeded its recruitment and crosstalk with PSCs. Our findings indicated that Dasatinib is a potential anti-inflammatory and anti-fibrotic therapeutic strategy for CP.

Background and aim Diabetes mellitus (DM) is a common complication of idiopathic chronic pancreatitis (ICP), which impairs the quality of life for patients. This study aimed to identify risk factors and develop nomogram for DM in ICP to help early diagnosis. Methods Idiopathic chronic pancreatitis patients admitted to our center from January 2000 to December 2013 were included. Cumulative rates of DM were calculated by Kaplan-Meier method. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on training cohort, risk factors for DM were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. Results Totally, 1633 patients with ICP were finally enrolled. The median follow-up duration was 9.8 years. DM was found in 26.3% (430/1633) of patients after the onset of CP. Adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct were identified risk factors for DM development. The nomogram achieved good concordance indexes in the training and validation cohorts, respectively, with well-fitted calibration curves. Conclusions Risk factors were identified, and nomogram was developed to determine the risk of DM in ICP patients. Patients with one or more of the risk factors including adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct have higher incidence of DM.

Background: Pancreatic stones are pathognomonic of chronic pancreatitis (CP). This study aimed to determine the incidence, identify risk factors, and develop a nomogram for pancreatic stones in CP patients. Methods: Patients with CP admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic stones after the onset of CP and after the diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. Results: With a total of 2,153 CP patients, pancreatic stones were detected in 1,626 (75.5%) patients, with a median follow-up of 7.8 years. Age at the onset of CP, body mass index, smoking, diabetes mellitus, pancreatic pseudocyst, biliary stricture, severe acute pancreatitis, and type of pain were identified risk factors for pancreatic stones development. The nomogram with these 8 factors achieved good accuracy. Conclusions: The nomogram achieved an individualized prediction of pancreatic stones development in CP. It may help the management of pancreatic stones.

BackgroundChronic pancreatitis (CP) is a chronic inflammatory disease of the pancreas. This study aimed to compare the natural course of alcoholic chronic pancreatitis (ACP) and idiopathic chronic pancreatitis (ICP).MethodsCP patients admitted to our center from January 2000 to December 2013 were enrolled. Characteristics were compared between ACP and ICP patients. Cumulative rates of diabetes mellitus (DM), steatorrhea, pancreatic stone, pancreatic pseudocyst, biliary stricture, and pancreatic cancer after the onset and the diagnosis of CP were calculated, respectively. The cumulative rates of DM and steatorrhea after diagnosis of pancreatic stone were also calculated.ResultsA total of 2,037 patients were enrolled. Among them, 19.8% (404/2,037) were ACP and 80.2% (1,633/2,037) were ICP patients. ACP and ICP differs in many aspects, especially in gender, age, smoking, complications, morphology of pancreatic duct, and type of pain. The development of DM, steatorrhea, PPC, pancreatic stone, and biliary stricture were significantly earlier and more common in ACP patients. No significant difference was observed for pancreatic cancer development. There was a rather close correlation between exocrine/endocrine insufficiency and pancreatic stone in ACP patients, which was much less correlated in ICP patients.ConclusionThe long-term profile of ACP and ICP differs in some important aspects. ACP patients usually have a more severe course of CP. These differences should be recognized in the diagnosis and treatment of CP.

This paper presents the test of 3 reinforced concrete pile caps and the complete procedure of failure as well as the stressed mechanism, including the description of the occurrence of cracks. The influences of reinforcement types on load-bearing capacity are also probed. A spatial truss model is put forward and can explain satisfactorily some phenomena observed in the test and the failure mechanism is investigated.

To identify the risk factors and develop nomograms for common bile duct (CBD) stricture in chronic pancreatitis (CP) patients.CBD stricture is a common complication in CP and has a variable clinical presentation ranging from asymptomatic to overt jaundice and cholangitis.Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of CBD stricture after onset and diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. On the basis of the training cohort, risk factors for CBD stricture and symptomatic CBD stricture were identified through Cox proportional hazards regression model, and nomograms was developed, respectively. Internal and external validations were performed based on the training and validation cohort, respectively.With a total of 2153 patients, the median duration of follow-up was 7.0 years. CBD strictures were detected in 340 (15.8%) patients, whereas 159 of them were symptomatic. Male gender, age at onset of CP, smoking, body mass index, and morphology of main pancreatic duct were identified risk factors for CBD stricture development. Age at onset of CP, body mass index, and type of pain were identified risk factors for symptomatic CBD stricture development. Both nomograms achieved good concordance indexes with well-fitted calibration curves.The nomogram achieved an individualized prediction of symptomatic CBD stricture development in CP patients. It may help the early diagnosis and intervention of symptomatic CBD stricture and reduce the rates of severe adverse events.

Background Risk of pancreatic cancer may increase in chronic pancreatitis patients. Aims This study aimed to identify the incidence of and risk factors for pancreatic cancer in chronic pancreatitis patients. Methods Chronic pancreatitis patients admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic cancer and survival rates were calculated. The standardized incidence ratio was calculated based on the pancreatic cancer incidence in general population of China. Risk factors for pancreatic cancer were identified. Results In a total of 1656 patients, the median follow-up duration was 8.0 years. Pancreatic cancer was detected in 21 patients (1.3%). The expected number of cases of pancreatic cancer was 1.039, yielding a standardized incidence ratio of 20.22. The standardized incidence ratios for patients with a >60 pack-year smoking history were much higher (145.82). Two risk factors for pancreatic cancer were identified: age at the onset of chronic pancreatitis (hazard ratio, 1.05) and a >60 pack-year smoking history (hazard ratio, 11.83). Conclusion The risk of pancreatic cancer is markedly increased in chronic pancreatitis patients compared with the general population, especially in patients with an older age at onset and a >60 pack-year smoking history. The high-risk populations were suggested to be followed up closely.

With the rapid development of Internet, Internet addiction has become a social issue of common concern. The different kinds of software have emerged to prevent Internet addiction. This paper analyzes and compares those software. A good prevention software should be good information filtering, to identify different kinds of content, web site, can be used to monitor and control the computer, not conflict with the anti-virus software or firewall, and not introduce other new vulnerabilities, not accounting for more memory and more network resources.

To study the clinical and neurological abnormalities in children with cerebral palsy (CP) and to attempt to correlate the types of CP and the gestational age at birth with radiological abnormalities detected by magnetic resonance imaging (MRI) of the brain.This is a hospital-based study, the subjects included 104 children with cerebral palsy who were hospitalized in the Qingdao Rehibilitation Center For Disabled Children. All the 104 hospitalized CP cases (47 with spastic diplegia, 9 with tetraplegia, 15 with hemiplegia, 22 with athetosis, and 11 with ataxia) were examined neurologically and their perinatal history was reviewed. Their cranial MRI findings were studied. The association between the gestational ages, CP types, and the radiological findings were studied.The type distribution was significantly different between term- and preterm- infants. Spastic diplegia was the main type in preterm infants while hemiplegia and ataxia were mainly seen in term infants. MRI abnormalities were found in 88 of the 104 cases and abnormal rates of spastic diplegia, tetraplegia, hemiplegia, athetosis, and ataxia were 89.4%, 100%, 100%, 54.5% and 90.9%, respectively. There was no significant difference in abnormal rates between term and preterm groups. Thirty-one of 42 (73.8%) children with spastic diplegia had significant periventricular leukomalacia (PVL), which was more common among preterm-born children (90%). Of the 15 children with hemiplegia, 13 had unilateral lesions on neuroimaging. Spastic tetraplegia was associated with extensive, bilateral, diffuse brain damage. The abnormalities in term-born infants with athetoid cerebral palsy were mainly located in the basal ganglia region whereas the major abnormality in premature infants was PVL. Of the 11 children with ataxic cerebral palsy, 8 cases showed congenital cerebellum dysplasia on brain imaging.Radiological abnormalities of the brain were correlated with CP types and the gestational age at birth; MRI scan was useful in revealing underlying brain abnormalities and speculating on the etiology of cerebral palsy.