In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.
Mice ; Animals ; Hedgehog Proteins/genetics* ; Receptors, G-Protein-Coupled/metabolism* ; Cilia/metabolism* ; Cartilage/metabolism* ; Regeneration

BACKGROUND: Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is a key protein that maintains myocardial Ca 2+ homeostasis. The present study aimed to investigate the mechanism underlying the SERCA2a-SUMOylation (small ubiquitin-like modifier) process after ischemia/reperfusion injury (I/RI) in vitro and in vivo . METHODS: Calcium transient and systolic/diastolic function of cardiomyocytes isolated from Serca2a knockout (KO) and wild-type mice with I/RI were compared. SUMO-relevant protein expression and localization were detected by quantitative real-time PCR (RT-qPCR), Western blotting, and immunofluorescence in vitro and in vivo . Serca2a-SUMOylation, infarct size, and cardiac function of Senp1 or Senp2 overexpressed/suppressed adenovirus infected cardiomyocytes, were detected by immunoprecipitation, triphenyltetrazolium chloride (TTC)-Evans blue staining, and echocardiography respectively. RESULTS: The results showed that the changes of Fura-2 fluorescence intensity and contraction amplitude of cardiomyocytes decreased in the I/RI groups and were further reduced in the Serca2a KO + I/RI groups. Senp1 and Senp2 messenger ribose nucleic acid (mRNA) and protein expression levels in vivo and in cardiomyocytes were highest at 6 h and declined at 12 h after I/RI. However, the highest levels in HL-1 cells were recorded at 12 h. Senp2 expression increased in the cytoplasm, unlike that of Senp1. Inhibition of Senp2 protein reversed the I/RI-induced Serca2a-SUMOylation decline, reduced the infarction area, and improved cardiac function, while inhibition of Senp1 protein could not restore the above indicators. CONCLUSION I/RI activated Senp1 and Senp2 protein expression, which promoted Serca2a-deSUMOylation, while inhibition of Senp2 expression reversed Serca2a-SUMOylation and improved cardiac function.
Animals ; Mice ; Calcium/metabolism* ; Cysteine Endopeptidases/metabolism* ; Myocardial Reperfusion Injury/metabolism* ; Myocardium/metabolism* ; Myocytes, Cardiac/metabolism* ; Proteins/metabolism* ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics*

Objective:To seek any correlation between and prognosis and hospitalization costs of stroke survivors with dysphagia.Methods:The records of 1370 stroke survivors admitted to the rehabilitation departments of 3 public hospitals in Weifang were studied. Of them, 499 (36.4%) were diagnosed with dysphagia and 871 were not. Binary logistic regression and multiple linear regression were employed to analyze the correlation between dysphagia and the occurrence of pneumonia, modified Rankin Scale (mRS) scores, modified Barthel index (MBI) scores, length of stay and total hospitalization cost.Results:After adjusting for confounding factors, the risk of pneumonia in the dysphagia group was 2.4 times higher. At discharge, the risk of an mRS≥3 was 3.3 times greater and that of an MBI score <60 was 1.7 times greater with dysphagia. Multiple stepwise linear regression showed that dysphagia was significantly associated with higher mRS scores at discharge, lower MBI scores, and longer hospital stays. The standardized regression coefficients predict that after the length of stay, dysphagia is the strongest predictor of the cost of hospitalisation, followed by ADL ability, pneumonia, supratentorial, haemorrhagic stroke and CCI.Conclusions:Dysphagia is a significant predictor of the hospitalization costs of stroke patients. It is recommended to identify and treat dysphagia as early as possible to improve the prognosis of such patients and reduce the economic burden.

Spinal cord injury (SCI) is a disabling and destructive central nervous system injury that has not yet been successfully treated at this stage. Three-dimensional (3D) bioprinting has become a promising method to produce more biologically complex microstructures, which fabricate living neural constructs with anatomically accurate complex geometries and spatial distributions of neural stem cells, and this is critical in the treatment of SCI. With the development of 3D printing technology and the deepening of research, neural tissue engineering research using different printing methods, bio-inks, and cells to repair SCI has achieved certain results. Although satisfactory results have not yet been achieved, they have provided novel ideas for the clinical treatment of SCI. Considering the potential impact of 3D bioprinting technology on neural studies, this review focuses on 3D bioprinting methods widely used in SCI neural tissue engineering, and the latest technological applications of bioprinting of nerve tissues for the repair of SCI are discussed. In addition to introducing the recent progress, this work also describes the existing limitations and highlights emerging possibilities and future prospects in this field.

OBJECTIVE: To analyze the clinical and genetic characteristics of a Chinese pedigree affected with developmental and epileptic encephalopathy 9. METHODS: N048: epilepsy full version gene detection panel-V2 and genome wide copy number variation analysis were carried out on the genomic DNA extracted from the peripheral blood samples. Amniotic fluid was also sampled for single nucleoticle polymorphism array (SNP-array) analysis. RESULTS: Both the mother and her daughter were found to have loss of heterozygosity at Xq21.31q22.1, with which exons of protocadherin 19 (PCDH19) gene was deleted. SNP-array showed the fetus to be a female and had arr[hg19]Xq21.31q22.1 (89 558 626-99 701 006)x1. The mother, daughter and fetus of this family all had developmental and epileptic encephalopathy 9. CONCLUSION Variant of the PCDH19 gene probably underlay the Developmental and epileptic encephalopathy 9 in this pedigree.
Cadherins/genetics* ; China ; DNA Copy Number Variations ; Epilepsy/genetics* ; Epilepsy, Generalized ; Female ; Humans ; Mutation ; Pedigree ; Protocadherins

Objective To investigate the occurrence and characteristics of dysphagia and aspiration in the elderly in nursing home in Weifang, Shandong, China.Methods From January to June, 2021, 837 elderly people from 10 nursing homes in Weifang were randomly selected and investigated with general situation questionnaire, Fried Frailty Phenotype, Ohkuma questionnaire and Volume-Viscosity Swallowing Test.Results The prevalence of dysphagia and aspiration was 44.2% and 12.3% respectively. There were significant differences in the prevalence of dysphagia among ages and health condition (χ2 > 8.437, P<0.05). The prevalence of dysphagia and aspiration was higher in men than in women (χ2 > 4.060, P < 0.05). The incidence of oral dysphagia was higher in men than in women, and the incidence of esophageal dysphagia was lower (χ2 > 20.830, P<0.001). Oral dysphagia was predominant in the elderly with stroke, Alzheimer's disease, and Parkinson's disease (χ2=27.579, P<0.001), and esophageal dysphagia and airway protection dysfunction were predominant in the elderly with chronic respiratory disease (χ2 > 20.241, P<0.01).Conclusion The dysphagia and aspiration are prevalent in the elderly in nursing homes, and varies with different genders and basic diseases.

OBJECTIVE：To establish the fingerprint of crude/vinegar-processed Corydalis yanhusuo decoction pieces and their dispensing granules，and to determine the contents of five alkaloids （protopine，tetrahydropalmatine，corydaline，berberine hydrochloride，palmatine hydrochloride ）. METHODS ：HPLC method was adopted. The determination was performed on Agilent TC-C18 column with mobile phase consisted of 0.1％ phosphoric acid solution-methanol （gradient elution ）at the flow rate of 1.0 mL/min. The detection wavelength was set at 280 nm，and the column temperature was 30 ℃. The sample size was 10 μL. Using palmatine hydrochloride as reference ， Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition） was used to establish the fingerprint of 11 059） batches of C. yanhusuo decoction pieces ，7 batches of crude . yanhusuo dispensing granules ， 12 batches of vinegar- processed C. yanhusuo decoction pieces and 11 batches of vinegar-processed C. yanhusuo dispensing granules. The same HPLC method was adopted to determine the contents of protopine， tetrahydropalmatine， corydaline， berberine hydrochloride and palmatine hydrochloride in 41 batches of crude/ vinegar-processed C. yanhusuo decoction pieces and their dispensing granules. RESULTS ：There were 12 and 20 common peaks for crude C. yanhusuo decoction pieces and its dispensing granules ，and 14 and 16 common peaks for vinegar-processed C. yanhusuo decoction pieces and its dispensing granules. The similarity of each batch of same type were 0.529-0.981，0.342-0.985， 0.711-0.999，0.437-0.998，respectively. The linear range of protopine ，tetrahydropalmatine，corydaline，berberine hydrochloride and palmatine hydrochloride were 1.9-38.0，2.0-40.0，2.2-44.0，2.6-52.0，2.3-46.0 μg/mL（R2＞0.999 0）. The recoveries were 100.12％-100.98％（RSD＝1.05％-1.90％，n＝9）. RSDs of precision ，reproducibility，stability（24 h）and durability tests were all lower than 2.0％. The average contents of five alkaloids in different batches of crude/vinegar-processed C. yanhusuo decoction pieces and its dispensing granules were 0.24-0.46，0.37-0.82，0.24-0.58，0.07-0.75，0.24-0.76 mg/g. RSDs were 12.27％-147.48％. CONCLUSIONS：The fingerprint of crude/vinegar-processed C. yanhusuo decoction pieces and its dispensing granules is established successfully. The similarities of fingerprint are different before and after processing with vinegar ，and the contents of five alkaloids in C. yanhusuo decoction pieces and its dispensing granules are greatly different.

Objective: The purpose is to explore the method and clinical effects of total nasal reconstruction with the assistance of three-dimensional (3D) scanning, 3D printing and monitoring the blood circulation after operation. Methods: 3D scanning: Artex Eva 3D scanner was used to record the nose data of 500 volunteers from Xuzhou Medical University and its affiliated hospital from September 2016 to February 2017. A nose database of normal individuals was established, of which male was 138 and female was 362. In addition, 3D facial scanning was performed in patients wish to total nasal reconstruction. 3D printing: The individualized nasal structure was designed, with the assistant of patients′facial characteristics, combined with the normal nose database and the opinion of the patients. Anactual nose model was used as guidance during the operation. Postoperative monitoring: The blood flow and the retraction rate of forehead flap after surgery were measured using Laser Doppler Flowmeter and Geomagic Qualify software. The blood flow values, the temperature and the surface area of the flap were recorded and analyzed. Results: The nasal database of normal people in the Huaihai region successfully established. Overall, the width of the nose takes up a quarter of the width of the faces, and the length is 1/3 of the distance from the hairline to the chin. From February 2017 to June 2018, 7 cases underwent total nasal reconstruction operations were performed by this procedure. The nasal models were all successfully printed out, as the guide of flap taken during the operation. The mean operation time of the cases was (2.45±0.75) h, and the follow-up time was 5-15 months, with an average of 12.5 months. After the operations, the retraction rate of the forehead flap were (21.8±2.72)% in one month, and (29.1±1.82)% in six months. All patients are satisfied with the nasal appearance. Conclusions Nasal reconstruction with forehead flap based on 3D scanning and 3D printing, provides objective targets for nasal fine-structure in a noninvasive way. The postoperative monitoring of the blood flow promotes the successful completion of the total nose reconstruction.

Objective To compare the clinical efficacy of aescuven fort and indomethacin in the prevention of heterotopic ossification (HO) after operative treatment of radial head fractures with anterior bundle of medial collateral ligament(AMCL) injury.Methods A total of 41 patients with radial head fracture combined with AMCL injury leading to elbow valgus instability were randomly divided into 21 cases of the observation group(aescuven fort) and the 20 cases of control group(indomethacin),and were treated with aescuven fort of 600rng/d and indomethacin of 75rng/d for 6 weeks respectively.The incidence of adverse reactions of gastrointestinal tract in the two groups was statistically analyzed,and symptomatic treatment was given.Six weeks later,the incidence of HO was recorded by X-ray examination of the elbow joint.The range of motion (ROM) was recorded,and the excellent and good rate of the improved HSS score was calculated.The results were statistically analyzed.Results The incidence rates of gastrointestinal side effects in the observation group and control group were 9.5％ and 35.0％,respectively,and the difference was statistically significant between the two groups(x2 =4.651,P =0.027).The incidence rate of HO in the observation groupwas 14.3％,which in the control group was 15.0％,there was no significant difference between the two groups(x2 =0.206,P =0.948).The ROM and excellent and good rate of the improved HSS score in the observation group and control group were [(119.2 ± 19.7) ° and 86.9％]and [(120.8 ± 16.3) ° and 88.7％],respectively,and the differences were statistically significant(t =2.023,P=0.613;x2 =0.176,P =0.675).Conclusion Aescuven fort can effectively prevent the formation of HO after operative treatment of radial head fracture with AMCL injury,similar with indomethacin.But the incidence rate of gastrointestinal side effects of aescuven fort is significantly lower than indomethacin.

Objective To investigate the significance of serum Let-7b in prostate cancer (PCa). Methods From July 2015 to September 2016, 72 patients with PCa (PCa group) and 34 healthy people (control group) were selected. The Let- 7b was detected by Western blot and fluorescence quantitative polymerase chain reaction (PCR), and the Let-7b was compared between 2 groups. Results The Let-7b in PCa group was significantly lower than that of control group (0.81 ±0.38 vs.1.31 ±0.34), and there was statistical difference (P<0.01). In PCa group, the Let- 7b in patients with TNM T3 and T4 stage was significantly lower than that in patients with TNM T1 and T2 stage (0.74 ± 0.39 vs. 0.88 ± 0.38), and there was statistical difference (P<0.05); the Let-7b in patients with hormone dependence was significantly higher than that in patients with hormone resistance (1.03 ± 0.40 vs. 0.64 ± 0.27), and there was statistical difference (P<0.05). Receiver operating characteristics curve analysis result showed that Let-7b sensitivity and specificity were 72.2％ and 88.2％ in the diagnosis of PCa. Conclusions Let-7b can indicate the degree of malignancy of the tumor and the hormone resistance. For patients with the high risk of early diagnosis of refractory PCa, the patients′ individualized treatment plan could be adjusted.