Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived car-diomyocytes(CMs)and an adult mouse model of myocardial infarction.HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,respectively.Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration.The results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent manner.As a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by hiPSC-CMs.GDF11 expression was unaffected by rhHapln1 treatment.However,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and proliferation.Recombinant mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial infarction.In addition,rmHapln1 induced hiPSC-CM proliferation.In conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway.Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a po-tential reagent for repairing damaged hearts.

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.
Mice ; Animals ; Epilepsy, Temporal Lobe/pathology* ; Parvalbumins/metabolism* ; Parkinson Disease/pathology* ; Neurons/metabolism* ; Interneurons/physiology* ; Disease Models, Animal ; Brain/pathology*

The modern surgical treatment of cervical degenerative disc disease can be traced back to the advent of anterior cervical decompression and fusion.With the emergence of fusion-related complications,different scholars have promoted the gradual transformation of cervical degenerative disc diseases from "fusion fixation" to "non-fusion reconstruction" through in-depth fusion with materials science,engineering mechanics and other disciplines.The innovation of this treatment concept is consistent with the original intention of "structural remodeling,functional reconstruction,maximum repair and reconstruction of the morphology and function of skeletal muscle system" in orthopedic bionic treatment,which is essentially in line with the "bionic alternative therapy" in orthopedic bionic therapy.This paper focuses on the surgical treatment of cervical degenerative disc diseases,reviews the development history of artificial cervical disc replacement,analyzes the evolution from orthopedic biomimetic therapy,and explores a new direction for the design of artificial cervical disc prostheses and the treatment of cervical degenerative disc diseases in the future.
Bionics ; Cervical Vertebrae/surgery* ; Diskectomy ; Follow-Up Studies ; Humans ; Intervertebral Disc/surgery* ; Intervertebral Disc Degeneration/surgery* ; Spinal Fusion ; Total Disc Replacement ; Treatment Outcome

Objective: To investigate the efficacy and safety of a new cervical artificial disc prosthesis in the treatment of cervical degenerative diseases. Methods: The clinical data of 18 patients with single-level cervical degenerative diseases who underwent three dimensional printed anatomical bionic cervical disc replacement at Department of Spinal Surgery,Honghui Hospital,Xi'an Jiaotong University from May 2019 to July 2020 were analyzed retrospectively. There were 7 males and 11 females,aged (45±8) years old(range:28 to 58 years).The surgical segment was located at C_3－4 level in 2 cases, C_4－5 level in 5 cases, C_5－6 level in 9 cases, and C_6－7 level in 2 cases.The clinical and radiographic outcomes were recorded and compared at preoperative,postoperative times of one month and twelve months.The clinical assessments contained Japanese orthopedic association (JOA) score,neck disability index (NDI) and visual analogue scale (VAS).Imaging assessments included range of motion (ROM) of cervical spine, prosthesis subsidence and prosthesis anteroposterior migration.Repeated measurement variance analysis was used for comparison between groups,and paired t test was used for pairwise comparison. Results: All patients underwent the operation successfully and were followed up for more than 12 months.Compared with preoperative score,the JOA score,NDI and VAS were significantly improved after surgery (all P<0.01).There was no significant difference in postoperative ROM compared with 1-and 12-month preoperative ROM (t=1.570,P=0.135;t=1.744,P=0.099). The prosthesis subsidence was (0.29±0.13) mm (range: 0.18 to 0.50 mm) at 12-month postoperatively.The migration of prosthesis at 12-months postoperatively were (0.71±0.20) mm (range: 0.44 to 1.08 mm).There was no prosthesis subsidence or migration>2 mm at 12-month postoperatively. Conclusion: Three dimensional printed anatomical biomimetic cervical artificial disc replacement has a good early clinical effect in the treatment of cervical degenerative diseases, good mobility can be obtained while maintaining stability.
Adult ; Biomimetics ; Cervical Vertebrae/surgery* ; Female ; Follow-Up Studies ; Humans ; Intervertebral Disc/surgery* ; Intervertebral Disc Degeneration/surgery* ; Male ; Middle Aged ; Range of Motion, Articular ; Retrospective Studies ; Total Disc Replacement/methods* ; Treatment Outcome

Background: Diminutive (≤5 mm) and small (6-9 mm) polyps are the most common colorectal polyps seen clinically, and a tiny percentage of them contain advanced histology. Aims: To clarify the endoscopic characteristics of diminutive and small colorectal polyps with advanced histology. Methods: A retrospective analysis was conducted in patients undergoing colonoscopic polypectomy in Ningbo First Hospital from June 2016 to September 2021, and the clinical, endoscopic and pathological data were collected. Propensity score matching (1: 1) was performed to select the non - advanced histology controls comparable with diminutive and small polyps with advanced histology. The endoscopic characteristics related to advanced histology was identified by univariate and multivariate analyses. Results: A total of 3 631 diminutive and small adenomatous polyps were detected in 2 950 patients, among them, 14 (1.2%) diminutive polyps and 114 (4.6%) small polyps were diagnosed as advanced histology pathologically, with 14 high - grade intraepithelial neoplasia (HGIN) in diminutive polyps, and 109 HGIN and 5 submucosal invasive carcinoma in small polyps. For serrated lesions, 755 polyps less than 10 mm in diameter were detected in 504 patients, but no advanced histology was diagnosed. Multivariate Logistic regression analysis showed that chicken skin mucosa (OR=3.790, 95% CI: 1.767-8.128), congestion (OR=2.802, 95% CI: 1.450 - 5.415), hemorrhage (OR=5.074, 95% CI: 1.511 - 17.035), lobular changes (OR=2.522, 95% CI: 1.247 - 5.098) and relative depression (OR=5.317, 95% CI: 1.376-20.550) were independent risk factors for advanced histology in diminutive and small polyps, while no correlations were found between JNET classification type 2B and type 3, Paris endoscopic classification type 0 - I and advanced histology. Conclusions: When endoscopic characteristics including chicken skin mucosa, congestion, hemorrhage, lobular changes and relative depression are found in diminutive and small colorectal polyps, advanced histology should be suspected.

Bone Cements ; Calcium ; Calcium Phosphates ; Materials Testing

Background: Reports on the efficacy of modifications to the thread design of pedicle screws are scarce. The aim of the study was to investigate initial and early fixation of pedicle screws with a plasma-sprayed titanium coating and dual pitch in the pedicle region (dual pitch titanium-coated pedicle screw [DPTCPS]) in a polyetheretherketone (PEEK) rod semi-rigid fixation system. Methods: Fifty-four sheep spine specimens and 64 sheep were used to investigate initial ( "0-week" controls) and early (postoperative 6 months) fixation, respectively. Sheep were divided into dual pitch pedicle screw (DPPS), standard pitch pedicle screw (SPPS), DPTCPS, and standard pitch titanium-coated pedicle screw (SPTCPS) groups. Specimens/sheep were instrumented with four screws and two rods. Biomechanical evaluations were performed, and histology at the implant-bone interface was investigated. Results: At 0-week, mean axial pull-out strength was significantly higher for the DPTCPS and SPTCPS than the SPPS (557.0 ± 25.2 vs. 459.1 ± 19.1 N, t = 3.61, P < 0.05; 622.6 ± 25.2 vs. 459.1 ± 19.1 N, t = 3.43, P < 0.05). On toggle-testing, the DPTCPS was significantly more resistant than the SPPS and SPTCPS (343.4 ± 16.5 vs. 237.5 ± 12.9 N, t = 3.52, P < 0.05; 343.4 ± 16.5 vs. 289.9 ± 12.8 N, t = 3.12, P < 0.05; 124.7 ± 13.5 vs. 41.9 ± 4.3 cycles, t = 2.18, P < 0.05; 124.7 ± 13.5 vs.79.5 ± 11.8 cycles, t = 2.76, P < 0.05). On cyclic loading, maximum displacement was significantly lower for the DPTCPS than the SPPS and SPTCPS (1.8 ± 0.13 vs. 3.76 ± 0.19 mm, t = 2.29, P < 0.05; 1.8 ± 0.13 vs. 2.46 ± 10.20 mm, t = 2.69, P < 0.05). At post-operative 6 months, mean axial pull-out strength was significantly higher for the DPTCPS and SPTCPS than the SPPS (908.4 ± 33.6 vs. 646.5 ± 59.4 N, t = 3.34, P < 0.05; 925.9 ± 53.9 vs. 646.5 ± 59.4 N, t = 3.37, P < 0.05). On toggle-testing, the DPTCPS was significantly more resistant than the SPPS and SPTCPS (496.9 ± 17.9 vs. 370.3 ± 16.4 N, t = 2.86, P < 0.05; 496.9 ± 17.9 vs. 414.1 ± 12.8 N, t = 2.74, P < 0.05; 249.1 ± 11.0 vs.149.9 ± 11.1 cycles, t = 2.54, P < 0.05; 249.1 ± 11.0 vs.199.8 ± 7.2 cycles, t = 2.61, P < 0.05). On cyclic loading, maximum displacement was significantly lower for the DPTCPS than the SPPS and SPTCPS (0.96 ± 0.11 vs. 2.39 ± 0.14 mm, t = 2.57, P < 0.05; 0.96 ± 0.11 vs. 1.82 ± 0.12 mm, t = 2.73, P < 0.05). Resistance to toggle testing (370.3 ± 16.4 vs. 414.1 ± 12.8 N, t = 3.29, P < 0.05; 149.9 ± 11.1 vs.199.8 ± 7.2 cycles, t = 2.97, P < 0.05) was significantly lower and maximum displacement in cyclic loading (2.39 ± 0.14 vs.1.82 ± 0.12 mm; t = 3.06, P < 0.05) was significantly higher for the SPTCPS than the DPTCPS. Bone-to-implant contact was significantly increased for the DPTCPS compared to the SPPS (58.3% ± 7.0% vs. 36.5% ± 4.4%, t = 2.74, P < 0.05); there was no inflammatory reaction or degradation of coated particles. Conclusion DPTCPSs might have stronger initial and early fixation in a PEEK rod semi-rigid fixation system.

Objective: To investigate the regularity in and risk factors for perioperative deep venous thrombosis (DVT) and the changes in plasma D-dimer in patients with tibiofibular fracture. Methods: A retrospective analysis was done of the 180 patients with tibiofibular fracture who had been treated at Department of Orthopaedics and Trauma, Xi'an Honghui Hospital from September 2014 to February 2018. They were 114 males and 66 females, aged from 16 to 83 years (average, 47.6 years). The levels of plasma D-dimer were detected at admission, one day preoperation, and 1, 3, 5 days postoperation. B-ultrasound examination of both lower extremities was performed before and after surgery. According to the results of B-ultrasound, the patients were divided into a DVT group and a non-DVT group. The 2 groups were compared in the plasma D-dimer levels measured at different time points. DVT risk factors were screened by univariate analysis, and multivariate logistic regression analysis was used to determine independent risk factors. Results: Of this cohort, 54 cases (30%) developed DVT and 39 cases (21.7%) did preoperation. Of the 39 cases (mixed DVT in one and distal DVT in 38 ones), DVT disappeared in 14 postoperation. Of the 40 cases (22.2%) of postoperative DVT (proximal DVT in one, mixed DVT in one and distal DVT in 38 ones), 15 developed newly postoperation. Multivariate logistic regression analysis showed that age, time from injury to operation, pre-operative and postoperative D-dimer elevation were independent risk factors for DVT in the patients. The D-dimer levels in the DVT group were significantly higher than in the non-DVT group at one day preoperation, and 1, 3, 5 days postoperation (P<0.05). The area under the receiver operating characteristic curve was 0.704. When the critical value of D-dimer was 1.4 mg/L, its sensitivity for DVT diagnosis was 0.944 and its specificity 0.246 (poor). When the concentration of D-dimer was 4.45 mg/L, its sensitivity for DVT diagnosis was 0.574 and its specificity 0.817 (the highest). Conclusions Perioperative DVT may happen in patients with tibiofibular fracture, mostly at the distal end beyond the popliteal vein. Clinically, patients who are advanced in age, have plasma D-dimer elevation at admission and after operation, and have waited long for operation should be alert to the occurrence of DVT. The plasma D-dimer level with a recommended threshold of 4.45 mg/L may have a certain diagnostic value for patients with tibiofibular fracture.

Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage (SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury (EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine (10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier (BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1β, IL-6, TNF-α, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.
Animals ; Apoptosis ; drug effects ; Blood-Brain Barrier ; drug effects ; Brain Edema ; drug therapy ; etiology ; Cytokines ; genetics ; metabolism ; Disease Models, Animal ; Fluoxetine ; pharmacology ; therapeutic use ; In Situ Nick-End Labeling ; Male ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Pain Measurement ; Psychomotor Performance ; drug effects ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; complications ; drug therapy ; pathology ; Time Factors ; Vasospasm, Intracranial ; drug therapy ; etiology