OBJECTIVE: To evaluate the safety and effectiveness of anterior cervical discectomy and fusion (ACDF) by using zero-profile anchored cage (ZAC) in treatment of consecutive three-level cervical spondylosis, by comparing with plate-cage construct (PCC). METHODS: A clinical data of 65 patients with cervical spondylosis admitted between January 2020 and December 2022 and met the selection criteria was retrospectively analyzed. During consecutive three-level ACDF, 35 patients were fixed with ZAC (ZAC group) and 30 patients with PCC (PCC group). There was no significant difference in baseline data between the two groups ( P>0.05), including gender, age, body mass index, surgical segment, preoperative Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI), visual analogue scale (VAS) score, prevertebral soft tissue thickness (PSTT), cervical lordosis, and surgical segmental angle. The operation time, intraoperative blood loss, hospital stay, clinical indicators (JOA score, NDI, VAS score), and radiological indicators (cervical lordosis, surgical segmental angle, implant subsidence, surgical segment fusion, and adjacent segment degeneration), and the postoperative complications [swelling of the neck (PSTT), dysphagia] were recorded and compared between the two groups. RESULTS: Patients in both groups were followed up 24-39 months. There was no significant difference in follow-up duration between the two groups ( P>0.05). The operation time and intraoperative blood loss were lower in ZAC group than in PCC group, and the length of hospital stay was longer, but there was no significant difference ( P>0.05). At each time point after operation, both groups showed significant improvements in JOA score, VAS score, and NDI compared with preoperative scores ( P<0.05), but there was no significant difference between the two groups at each time point after operation ( P>0.05). Both groups showed an increase in PSTT at 3 days and 3, 6 months after operation compared to preoperative levels ( P<0.05), but returned to preoperative levels at last follow-up ( P>0.05). The PSTT at 3 days and 3 months after operation were significantly lower in ZAC group than in PCC group ( P<0.05), and there was no significant difference between the two groups at 6 months and at last follow-up ( P>0.05). The incidences of dysphagia at 3 days and 3 months were significantly lower in ZAC group than in PCC group ( P<0.05), while no significant difference was observed at 6 months and last follow-up between the two groups ( P>0.05). There was no postoperative complication in both groups including hoarseness, esophageal injury, cough, or hematoma. Both groups showed improvement in cervical lordosis and surgical segmental angle compared to preoperative levels, with a trend of loss during follow-up. The cervical lordosis loss and surgical segmental angle loss were significantly more in the ZAC group than in PCC group ( P<0.05). The incidence of implante subsidence was significantly higher in ZAC group than in PCC group ( P<0.05). There was no significant difference between the ZAC group and PCC group in the incidences of surgical segment fusion and adjacent segment degeneration ( P>0.05). CONCLUSION In consecutive three-level ACDF, both ZAC and PCC can achieve satisfactory effectiveness. The former can reduce the incidence of postoperative dysphagia, while the latter can better maintain cervical curvature and reduce the incidence of implant subsidence.
Humans ; Spondylosis/surgery* ; Cervical Vertebrae/surgery* ; Spinal Fusion/instrumentation* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Diskectomy/instrumentation* ; Bone Plates ; Treatment Outcome ; Adult ; Aged ; Internal Fixators ; Operative Time ; Length of Stay

Aging is a physiological process characterized by the gradual decline of the body's functions over time.In recent years, the emergence of molecular hydrogen(H 2)medicine has introduced novel approaches to the field of anti-aging.Numerous animal experiments and clinical trials have demonstrated that H 2 possesses considerable potential to regulate oxidative stress, inflammation, organelle energy metabolism, and programmed cell death, while also offering protective effects on various organs and systems.Currently, H 2 is being utilized in the prevention and treatment of various age-related diseases, thereby opening new avenues for anti-aging interventions.

Aging is a physiological process characterized by the gradual decline of the body's functions over time.In recent years, the emergence of molecular hydrogen(H 2)medicine has introduced novel approaches to the field of anti-aging.Numerous animal experiments and clinical trials have demonstrated that H 2 possesses considerable potential to regulate oxidative stress, inflammation, organelle energy metabolism, and programmed cell death, while also offering protective effects on various organs and systems.Currently, H 2 is being utilized in the prevention and treatment of various age-related diseases, thereby opening new avenues for anti-aging interventions.

BACKGROUND:The most prominent transcription factor activated by tumor stem cells in osteosarcoma is EZH2,and silencing of EZH2 has been reported to inhibit osteosarcoma cell growth.Studies have confirmed that bovine serum albumin-chitosan nanoparticles are a drug delivery vector with excellent biocompatibility and biodegradability,and the albumin carrier can provide tumor-targeted drug delivery function. OBJECTIVE:To investigate the effect and mechanism of bovine serum albumin-chitosan nanoparticles loaded with EPZ6438(EZH2 inhibitor)for the treatment of osteosarcoma. METHODS:(1)Bovine serum albumin-chitosan nanoparticles loaded with and without EPZ6438 were prepared.The drug encapsulation rate and drug release rate of serum albumin-chitosan nanoparticles loaded with EPZ6438 were detected.(2)MG-63 cells were divided into four groups and added with PBS(control group),serum albumin-chitosan nanoparticle extract solution(blank nanoparticle group),EPZ6438 solution(free drug group),and serum albumin-chitosan nanoparticle extract loaded with EPZ6438(drug-loaded nanoparticle group),respectively.After 3 days of culture,cell apoptosis was detected by flow cytometry and the expression of caspase-3 mRNA was detected by RT-PCR.(3)Twelve nude mice were selected and the subcutaneous tumor-bearing mouse model was established by injecting MG-63 cell suspension under the armpit.After successful modeling,the mice were randomly divided into four groups for intervention.Normal saline(control group),serum albumin-chitosan nanoparticle solution(blank nanoparticle group),EPZ6438 solution(free drug group)and serum albumin-chitosan nanoparticle solution loaded with EPZ6438(drug-loaded nanoparticle group)were injected into tumor tissues,with three animals in each group.After 7 days of injection,the tumor volume and frozen sections of tumor tissue were observed by TUNEL staining. RESULTS AND CONCLUSION:(1)The drug encapsulation rate of the nanoparticles was about 8.8%,and the nanoparticles had a good drug release effect in pure water.The drug release amount was(34.72±1.93)μg at 24 hours,(48.58±1.10)μg at 72 hours,(49.18±1.24)μg at 120 hours,and(50.25±1.13)μg at 168 hours.The drug release reached the plateau at 120 hours,and the release rate was about 97.9%.(2)After 3 days of cell culture with MG-63,the apoptotic rate in the control group and blank nanoparticle group was lower than that in the free drug group and drug-loaded nanoparticle group(P<0.001),and the expression of caspase 3 mRNA was lower than that in the free drug group and drug-loaded nanoparticle group(P<0.000 1).(3)After 7 days of injection,the tumor volume of nude mice in the drug-loaded nanoparticle group was smaller than that in the other three groups(P<0.05),and the percentage of TUNEL-positive cells in tumor tissue was higher than that in the other three groups(P<0.000 1).(4)The results verify that serum albumin-chitosan nanoparticles loaded with EPZ6438 can inhibit the growth of osteosarcoma by inducing apoptosis of tumor cells.

GPCRs are the largest membrane protein receptor superfamily in the human body, with more than 800 isoforms, and approximately 35% of Food and Drug Administration-approved and marketed drugs currently target GPCRs for the treatment of a wide range of diseases, for heart failure (beta-adrenergic receptors), peptic ulcer (histamine receptors), prostate cancer (gonadotropin receptors), hypertension (adrenergic and angiotensin receptors), pain (opioid receptors), and bronchial asthma (beta2-adrenergic receptors) examples. Although the number of GPCRs is enormous, the signaling proteins downstream of them are limited, heterotrimeric G proteins (GPs) are key proteins that signal GPCRs, translate extracellular stimuli into intracellular responses by coupling to GPCRs and initiate multiple signaling events via downstream cascades. Podocytes are an important component of the glomerular filtration barrier, and their damage is a central event in proteinuria formation and progressive glomerulosclerosis. This article reviews the regulation of GPs, their signaling and their role in podocyte injury to provide a theoretical basis for scientific research and clinical treatment of this disease.

ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Taking Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology as an example,it discusses the basic ideas and innovative practices of project organization from"passive order taking"to"active planning",platform construction from"free growth"to"directional cultivation",team construction from"wearing hats"to"focusing on actual combat",and achievement transformation from"resource guidance"to"comprehensive policy".It puts forward some suggestions that hospitals should play the leading role of"national team"in organizing scientific research and innovation practice,pay attention to the docking of national strategy,the linkage of university resources.

Objective To investigate the interventional effects of Icariin(IC A)combined with prednisone acetate tablets(PAT)in rats with steroid-resistant nephrotic syndrome(SRNS)model.Methods Male SD rats were used to construct the SRNS model with 2 injections of adriamycin(ADR),and were randomly divided into the model group,PAT group,ICA group,and the combined group,with 10 rats in each group after successful modeling;another 10 rats were taken as the blank group.The blank and model groups were given 0.9％NaCl;the PAT group was given 6.3 mg·kg-1·d-1 PAT;the ICA group was given 50 mg·kg-1·d-1 ICA;and the combined group was given 6.3 mg·kg-1·d-1 PAT+50 mg·kg-1·d-1 ICA.The volume of gavage of the five groups of rats was 1 mL·100 g-1,and the drug was administered once a day for 6 weeks.The renal function and blood lipid level of rats in each group were compared;the expression of calcium/calmodulin dependent protein kinase Ⅱ α(CaMK Ⅱα),cofilin-1 and F-actin were detected by Western blotting.Results Urinary protein quantification values at 8 weeks in blank,model,PAT,ICA and combined groups were(6.66±1.48),(178.38±8.96),(161.56±5.49),(157.13±8.32)and(96.90±5.05)mg·24 hi-1;serum creatinine levels were(30.90±1.79),(41.10±2.77),(34.90±2.03),(35.10±2.18)and(31.90±2.47)μmol·L-1;triglycerides levels were(0.87±0.14),(2.30±0.41),(1.94±0.44),(1.17±0.59)and(0.89±0.30)mmol·L-1;total cholesterol levels were(1.54±0.08),(2.53±0.22),(2.14±0.59),(2.27±0.31)and(1.93±0.32)mmol·L-1;the relative expression levels of CaMK Ⅱ α proteins were 0.88±0.09,0.65±0.06,0.71±0.08,0.76±0.07 and 0.88±0.08;the p-Cofilin-1/Cofilin-1 ratios were 0.56±0.27,2.52±0.04,0.75±0.02,0.91±0.20 and 0.53±0.05;the relative expression levels of F-actin protein were 0.93±0.01,0.64±0.01,0.75±0.02,0.80±0.01 and 0.85±0.00,respectively.The differences of the above indexes in the model group were statistically significant compared with those in the blank group and the combined group(all P＜0.05).Conclusion ICA combined with PAT can improve renal function,lipid levels,improve renal histopathological structure,and promote skeletal protein remodeling in SRNS rats by regulating CaMK Ⅱ α/Cofilin-1/F-actin pathway.

Renal fibrosis is a common pathological manifestation of all chronic kidney diseases.Ferroptosis is closely related to the pathogenesis of renal fibrosis and can influence the onset of renal fibrosis,and it is the most critical step in the development of renal fibrosis.The paper describes the relationship between ferroptosis and renal fibrosis,discusses the research progress of ferroptosis on renal fibrosis,and further summarizes,analyzes,and describes the effective and highly targeted natural active ingredients of traditional Chinese medicines against ferroptosis,and concludes that the reversal of renal fibrosis is achieved through the regulation of the key targets of ferroptosis,with a view to providing a broad new direction for its prospects in the field of renal fibrotic disease prevention and treatment;and to provide a scientific guide for clinical treatment and basis for clinical treatment.